Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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16 pages, 2598 KiB  
Article
Identifying Knowledge Gaps through the Systematic Review of Temperature-Driven Variability in the Competence of Aedes aegypti and Ae. albopictus for Chikungunya Virus
by Rebecca C. Christofferson, Erik A. Turner and Víctor Hugo Peña-García
Pathogens 2023, 12(11), 1368; https://doi.org/10.3390/pathogens12111368 - 18 Nov 2023
Viewed by 1464
Abstract
Temperature is a well-known effector of several transmission factors of mosquito-borne viruses, including within mosquito dynamics. These dynamics are often characterized by vector competence and the extrinsic incubation period (EIP). Vector competence is the intrinsic ability of a mosquito population to become infected [...] Read more.
Temperature is a well-known effector of several transmission factors of mosquito-borne viruses, including within mosquito dynamics. These dynamics are often characterized by vector competence and the extrinsic incubation period (EIP). Vector competence is the intrinsic ability of a mosquito population to become infected with and transmit a virus, while EIP is the time it takes for the virus to reach the salivary glands and be expectorated following an infectious bloodmeal. Temperatures outside the optimal range act on life traits, decreasing transmission potential, while increasing temperature within the optimal range correlates to increasing vector competence and a decreased EIP. These relatively well-studied effects of other Aedes borne viruses (dengue and Zika) are used to make predictions about transmission efficiency, including the challenges presented by urban heat islands and climate change. However, the knowledge of temperature and chikungunya (CHIKV) dynamics within its two primary vectors—Ae. aegypti and Ae. albopictus—remains less characterized, even though CHIKV remains a virus of public-health importance. Here, we review the literature and summarize the state of the literature on CHIKV and temperature dependence of vector competence and EIP and use these data to demonstrate how the remaining knowledge gap might confound the ability to adequately predict and, thus, prepare for future outbreaks. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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11 pages, 1576 KiB  
Article
Predominance of Canine Parainfluenza Virus and Mycoplasma in Canine Infectious Respiratory Disease Complex in Dogs
by Aurelle Yondo, Allen A. Kalantari, Ingrid Fernandez-Marrero, Amy McKinney, Hemant K. Naikare and Binu T. Velayudhan
Pathogens 2023, 12(11), 1356; https://doi.org/10.3390/pathogens12111356 - 15 Nov 2023
Viewed by 1541
Abstract
Canine infectious respiratory disease complex (CIRDC) is caused by different viruses and bacteria. Viruses associated with CIRDC include canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine herpesvirus type 1 (CHV-1), canine respiratory coronavirus (CRCoV), and canine parainfluenza [...] Read more.
Canine infectious respiratory disease complex (CIRDC) is caused by different viruses and bacteria. Viruses associated with CIRDC include canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine herpesvirus type 1 (CHV-1), canine respiratory coronavirus (CRCoV), and canine parainfluenza virus (CPIV). Bacteria associated with CIRDC include Bordetella bronchiseptica, Streptococcus equi subspecies zooepidemicus (S. zooepidemicus), and Mycoplasma spp. The present study examined the prevalence of CIRDC pathogens in specimens received by a Veterinary Diagnostic Laboratory in Georgia, USA., from 2018 to 2022. Out of 459 cases, viral agents were detected in 34% of cases and bacterial agents were detected in 58% of cases. A single pathogen was detected in 31% of cases, while two or more pathogens were identified in 24% of cases. The percentages of viral agents identified were CAV-2 (4%), CDV (3%), CPIV (16%), CRCoV (7%), and CIV (2%). The percentages of bacterial agents were B. bronchiseptica (10%), Mycoplasma canis (24%), Mycoplasma cynos (21%), and S. zooepidemicus (2%). Over the five-year period, the positive cases ranged from 2–4% for CAV-2, 1–7% for CDV, 1–4% for CHV-1, 9–22% for CPIV, 4–13% for CRCoV, and 1–4% for CIV. Overall, the most prevalent pathogens associated with CIRDC were CPIV, M. canis, and M. cynos. Full article
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16 pages, 717 KiB  
Article
Cervical HPV Infections, Sexually Transmitted Bacterial Pathogens and Cytology Findings—A Molecular Epidemiology Study
by George Valasoulis, Abraham Pouliakis, Georgios Michail, Ioulia Magaliou, Christos Parthenis, Niki Margari, Christine Kottaridi, Aris Spathis, Danai Leventakou, Argyro-Ioanna Ieronimaki, Georgios Androutsopoulos, Periklis Panagopoulos, Alexandros Daponte, Sotirios Tsiodras and Ioannis G. Panayiotides
Pathogens 2023, 12(11), 1347; https://doi.org/10.3390/pathogens12111347 - 14 Nov 2023
Cited by 1 | Viewed by 1090
Abstract
Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the [...] Read more.
Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years (p < 0.05)) was associated with negative STI testing. Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI (OR: 2.69, 95% CI 2.10–3.46, p < 0.05). Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation. Full article
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26 pages, 8053 KiB  
Article
Polyinfection in Fish Aeromoniasis: A Study of Co-Isolated Aeromonas Species in Aeromonas veronii Outbreaks
by Yanelys Cantillo Villa, Adriana Triga and Pantelis Katharios
Pathogens 2023, 12(11), 1337; https://doi.org/10.3390/pathogens12111337 - 10 Nov 2023
Viewed by 1639
Abstract
We studied the phenotypic and genomic characteristics related to the virulence and antibiotic resistance of two Aeromonas strains, which were co-isolated before an outbreak of Aeromonas veronii among diseased seabass on Agathonisi Island, Greece, in April 2015. The first strain, AG2.13.2, is a [...] Read more.
We studied the phenotypic and genomic characteristics related to the virulence and antibiotic resistance of two Aeromonas strains, which were co-isolated before an outbreak of Aeromonas veronii among diseased seabass on Agathonisi Island, Greece, in April 2015. The first strain, AG2.13.2, is a potentially pathogenic mesophilic variant of Aeromonas salmonicida, and the second, AG2.13.5, corresponds to an Aeromonas rivipollensis related to A. rivipollensis KN-Mc-11N1 with an ANI value of 97.32%. AG2.13.2 lacks the type III secretion system just like other mesophilic strains of A. salmonicida. This characteristic has been associated with lower virulence. However, the genome of AG2.13.2 contains other important virulence factors such as type II and type VI secretion systems, and toxins such as rtxA, aerolysin aer/act, and different types of hemolysins. The strain also carries several genes associated with antibiotic resistance such as the tetE efflux pump, and exhibits resistance to tetracycline, ampicillin, and oxolinic acid. In an in vivo challenge test with gilthead seabream larvae, the A. veronii bv sobria strain AG5.28.6 exhibited the highest virulence among all tested strains. Conversely, both A. salmonicida and A. rivipollensis showed minimal virulence when administered alone. Interestingly, when A. veronii bv sobria AG5.28.6 was co-administered with A. rivipollensis, the larvae survival probability increased compared to those exposed to A. veronii bv sobria AG5.28.6 alone. This finding indicates an antagonistic interaction between A. veronii bv sobria AG5.28.6 and A. rivipollensis AG2.13.5. The co-administration of A. veronii bv sobria AG5.28.6 with Aeromonas salmonicida did not yield distinct survival probabilities. Our results validate that the primary pathogen responsible for European seabass aeromoniasis is Aeromonas veronii bv sobria. Full article
(This article belongs to the Special Issue Aeromonas: Genome, Transmission, Pathogenesis, and Treatment)
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35 pages, 17627 KiB  
Article
The Cultured Microbiome of Pollinated Maize Silks Shifts after Infection with Fusarium graminearum and Varies by Distance from the Site of Pathogen Inoculation
by Michelle E. H. Thompson, Anuja Shrestha, Jeffrey Rinne, Victor Limay-Rios, Lana Reid and Manish N. Raizada
Pathogens 2023, 12(11), 1322; https://doi.org/10.3390/pathogens12111322 - 06 Nov 2023
Viewed by 2159
Abstract
Styles transmit pollen-derived sperm nuclei from pollen to ovules, but also transmit environmental pathogens. The microbiomes of styles are likely important for reproduction/disease, yet few studies exist. Whether style microbiome compositions are spatially responsive to pathogens is unknown. The maize pathogen Fusarium graminearum [...] Read more.
Styles transmit pollen-derived sperm nuclei from pollen to ovules, but also transmit environmental pathogens. The microbiomes of styles are likely important for reproduction/disease, yet few studies exist. Whether style microbiome compositions are spatially responsive to pathogens is unknown. The maize pathogen Fusarium graminearum enters developing grain through the style (silk). We hypothesized that F. graminearum treatment shifts the cultured transmitting silk microbiome (TSM) compared to healthy silks in a distance-dependent manner. Another objective of the study was to culture microbes for future application. Bacteria were cultured from husk-covered silks of 14 F. graminearum-treated diverse maize genotypes, proximal (tip) and distal (base) to the F. graminearum inoculation site. Long-read 16S sequences from 398 isolates spanned 35 genera, 71 species, and 238 OTUs. More bacteria were cultured from F. graminearum-inoculated tips (271 isolates) versus base (127 isolates); healthy silks were balanced. F. graminearum caused a collapse in diversity of ~20–25% across multiple taxonomic levels. Some species were cultured exclusively or, more often, from F. graminearum-treated silks (e.g., Delftia acidovorans, Klebsiella aerogenes, K. grimontii, Pantoea ananatis, Stenotrophomonas pavanii). Overall, the results suggest that F. graminearum alters the TSM in a distance-dependent manner. Many isolates matched taxa that were previously identified using V4-MiSeq (core and F. graminearum-induced), but long-read sequencing clarified the taxonomy and uncovered greater diversity than was initially predicted (e.g., within Pantoea). These isolates represent the first comprehensive cultured collection from pathogen-treated maize silks to facilitate biocontrol efforts and microbial marker-assisted breeding. Full article
(This article belongs to the Special Issue Current Research on Fusarium: 2nd Edition)
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14 pages, 743 KiB  
Article
Clinical Characteristics of Neurocysticercosis in a Peruvian Population-Based Epilepsy Cohort: A Descriptive Cross-Sectional Study of Baseline Clinical Intake
by Samantha E. Allen, Luz M. Moyano, Melissa T. Wardle, Carolina Guzman, Sofia S. Sanchez-Boluarte, Gabrielle Bonnet, Javier A. Bustos, Seth O’Neal and Hector H. Garcia
Pathogens 2023, 12(11), 1313; https://doi.org/10.3390/pathogens12111313 - 03 Nov 2023
Cited by 1 | Viewed by 1046
Abstract
(1) Background: This study presents the baseline characteristics of a community-level population of people with epilepsy (n = 1975) living in an area endemic for Taenia solium, the pathogen responsible for neurocysticercosis (NCC). (2) Methods: Participants were sequentially enrolled in a clinical [...] Read more.
(1) Background: This study presents the baseline characteristics of a community-level population of people with epilepsy (n = 1975) living in an area endemic for Taenia solium, the pathogen responsible for neurocysticercosis (NCC). (2) Methods: Participants were sequentially enrolled in a clinical cohort from 2007 to 2020 in Tumbes, Peru. All participants provided demographic and clinical history and received clinical evaluations. Diagnostics, including neuroimaging, cysticercosis serologies, and EEG, were obtained where possible. The data presented are from the cross-sectional baseline assessment of cohort participants. (3) Results: Approximately 38% of participants met the criteria for NCC. Those with NCC were more likely to have adult-onset epilepsy, as well as a longer duration of epilepsy, as compared to their counterparts without NCC. Overall, the data indicate a large treatment gap, with only approximately a quarter of the baseline population with prescriptions for anti-seizure medications. (4) Conclusions: These data reveal a high proportion of NCC among people living with epilepsy in these communities, with limited health care resources. At baseline, 74% of the population were not receiving anti-seizure treatments. Further analyses of these data will clarify the natural history of the disease for this population. Full article
(This article belongs to the Special Issue Recent Advances in Taeniasis and Cysticercosis)
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11 pages, 875 KiB  
Article
Prevalence and Molecular Characterization of Shiga Toxin-Producing Escherichia coli from Food and Clinical Samples
by Khulud Alotaibi and Ashraf A. Khan
Pathogens 2023, 12(11), 1302; https://doi.org/10.3390/pathogens12111302 - 31 Oct 2023
Viewed by 1262
Abstract
Shiga toxin-producing Escherichia coli (STEC) is one of the most prominent food-borne pathogens in humans. The current study aims to detect and to analyze the virulence factors, antibiotic resistance, and plasmid profiles for forty-six STEC strains, isolated from clinical and food strains. Pulsed-field [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) is one of the most prominent food-borne pathogens in humans. The current study aims to detect and to analyze the virulence factors, antibiotic resistance, and plasmid profiles for forty-six STEC strains, isolated from clinical and food strains. Pulsed-field gel electrophoresis (PFGE) was used to determine the genetic relatedness between different serotypes and sources of samples. The clinical samples were found to be resistant to Nb (100%), Tet (100%), Amp (20%), SXT (15%), and Kan (15%) antibiotics. In contrast, the food strains were found to be resistant to Nb (100%), Tet (33%), Amp (16.6%), and SXT (16.6%) antibiotics. The PFGE typing of the forty-six isolates was grouped into more than ten clusters, each with a similarity between 30% and 70%. Most of the isolates were found positive for more than five virulence genes (eae, hlyA, stx1, stx2, stx2f, stx2c, stx2e, stx2, nelB, pagC, sen, toxB, irp, efa, and efa1). All the isolates carried different sizes of the plasmids. The isolates were analyzed for plasmid replicon type by PCR, and 72.5% of the clinical isolates were found to contain X replicon-type plasmid, 50% of the clinical isolates contained FIB replicon-type plasmid, and 17.5% of the clinical isolates contained Y replicon-type plasmid. Three clinical isolates contained both I1 and Hi1 replicon-type plasmid. Only two food isolates contained B/O and W replicon-type plasmid. These results indicate that STEC strains have diverse clonal populations among food and clinical strains that are resistant to several antimicrobials. In conclusion, our findings indicate that food isolates of STEC strains harbor virulence, antimicrobial resistance, plasmid replicon typing determinants like those of other STEC strains from clinical strains. These results suggest that these strains are unique and may contribute to the virulence of the isolates. Therefore, surveillance and characterization of STEC strains can provide useful information about the prevalence of STEC in food and clinical sources. Furthermore, it will help to identify STEC serotypes that are highly pathogenic to humans and may emerge as a threat to public health. Full article
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20 pages, 2843 KiB  
Review
Drug-Resistant Aspergillus spp.: A Literature Review of Its Resistance Mechanisms and Its Prevalence in Europe
by Maria Antonia De Francesco
Pathogens 2023, 12(11), 1305; https://doi.org/10.3390/pathogens12111305 - 31 Oct 2023
Cited by 1 | Viewed by 1353
Abstract
Infections due to the Aspergillus species constitute an important challenge for human health. Invasive aspergillosis represents a life-threatening disease, mostly in patients with immune defects. Drugs used for fungal infections comprise amphotericin B, triazoles, and echinocandins. However, in the last decade, an increased [...] Read more.
Infections due to the Aspergillus species constitute an important challenge for human health. Invasive aspergillosis represents a life-threatening disease, mostly in patients with immune defects. Drugs used for fungal infections comprise amphotericin B, triazoles, and echinocandins. However, in the last decade, an increased emergence of azole-resistant Aspergillus strains has been reported, principally belonging to Aspergillus fumigatus species. Therefore, both the early diagnosis of aspergillosis and its epidemiological surveillance are very important to establish the correct antifungal therapy and to ensure a successful patient outcome. In this paper, a literature review is performed to analyze the prevalence of Aspergillus antifungal resistance in European countries. Amphotericin B resistance is observed in 2.6% and 10.8% of Aspergillus fumigatus isolates in Denmark and Greece, respectively. A prevalence of 84% of amphotericin B-resistant Aspergillus flavus isolates is reported in France, followed by 49.4%, 35.1%, 21.7%, and 20% in Spain, Portugal, Greece, and amphotericin B resistance of Aspergillus niger isolates is observed in Greece and Belgium with a prevalence of 75% and 12.8%, respectively. The prevalence of triazole resistance of Aspergillus fumigatus isolates, the most studied mold obtained from the included studies, is 0.3% in Austria, 1% in Greece, 1.2% in Switzerland, 2.1% in France, 3.9% in Portugal, 4.9% in Italy, 5.3% in Germany, 6.1% in Denmark, 7.4% in Spain, 8.3% in Belgium, 11% in the Netherlands, and 13.2% in the United Kingdom. The mechanism of resistance is mainly driven by the TR34/L98H mutation. In Europe, no in vivo resistance is reported for echinocandins. Future studies are needed to implement the knowledge on the spread of drug-resistant Aspergillus spp. with the aim of defining optimal treatment strategies. Full article
(This article belongs to the Section Fungal Pathogens)
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9 pages, 757 KiB  
Article
The Presence of a Parasite in the Head Tissues of a Threatened Fish (Bidyanus bidyanus, Terapontidae) from South-Eastern Australia
by Diane P. Barton, R. Keller Kopf, Xiaocheng Zhu and Shokoofeh Shamsi
Pathogens 2023, 12(11), 1296; https://doi.org/10.3390/pathogens12111296 - 30 Oct 2023
Viewed by 979
Abstract
The silver perch, Bidyanus bidyanus (Mitchell) (Terapontidae) is a freshwater fish, endemic to the Murray-Darling river system in south-eastern Australia. Population declines have led to the fish being listed as critically endangered by the Australian Government. Knowledge about parasites and diseases of wild [...] Read more.
The silver perch, Bidyanus bidyanus (Mitchell) (Terapontidae) is a freshwater fish, endemic to the Murray-Darling river system in south-eastern Australia. Population declines have led to the fish being listed as critically endangered by the Australian Government. Knowledge about parasites and diseases of wild populations of freshwater fish are limited in Australia. During an examination of wild-caught silver perch, digenean mesocercaria were observed in the head tissues. A total of five of the 11 silver perch collected from the Wakool River, New South Wales, were infected with mesocercaria. All mesocercaria were found in the head tissues; no mesocercaria were found encysted in the eye lens. The mesocercaria were found to belong to the family Strigeidae based on the sequences of their internal transcribed spacer (ITS) region. The lack of comparable sequences of strigeid digeneans from Australian hosts precludes being able to determine if the mesocercaria found in this study are a new species or representatives of an already described species. However, genetic results confirm that this is a different species to other digeneans previously described from silver perch, thus increasing the number of digeneans reported from B. bidyanus to three species. The presence of digenean mesocercaria in the head tissues of a wild population of silver perch, as found in the present study, is of potential conservation significance. Given the critically endangered conservation status of B. bidyanus, and previous evidence of strigeid infection altering fish behaviour, ecology, and predation mortality, further research on the potential impacts of infection on wild populations is warranted. Full article
(This article belongs to the Special Issue Aquatic Parasites)
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12 pages, 335 KiB  
Review
Interactions between West Nile Virus and the Microbiota of Culex pipiens Vectors: A Literature Review
by Marta Garrigós, Mario Garrido, Guillermo Panisse, Jesús Veiga and Josué Martínez-de la Puente
Pathogens 2023, 12(11), 1287; https://doi.org/10.3390/pathogens12111287 - 27 Oct 2023
Cited by 2 | Viewed by 1391
Abstract
The flavivirus West Nile virus (WNV) naturally circulates between mosquitoes and birds, potentially affecting humans and horses. Different species of mosquitoes play a role as vectors of WNV, with those of the Culex pipiens complex being particularly crucial for its circulation. Different biotic [...] Read more.
The flavivirus West Nile virus (WNV) naturally circulates between mosquitoes and birds, potentially affecting humans and horses. Different species of mosquitoes play a role as vectors of WNV, with those of the Culex pipiens complex being particularly crucial for its circulation. Different biotic and abiotic factors determine the capacity of mosquitoes for pathogen transmission, with the mosquito gut microbiota being recognized as an important one. Here, we review the published studies on the interactions between the microbiota of the Culex pipiens complex and WNV infections in mosquitoes. Most articles published so far studied the interactions between bacteria of the genus Wolbachia and WNV infections, obtaining variable results regarding the directionality of this relationship. In contrast, only a few studies investigate the role of the whole microbiome or other bacterial taxa in WNV infections. These studies suggest that bacteria of the genera Serratia and Enterobacter may enhance WNV development. Thus, due to the relevance of WNV in human and animal health and the important role of mosquitoes of the Cx. pipiens complex in its transmission, more research is needed to unravel the role of mosquito microbiota and those factors affecting this microbiota on pathogen epidemiology. In this respect, we finally propose future lines of research lines on this topic. Full article
(This article belongs to the Special Issue West Nile Virus and Other Zoonotic Infections)
22 pages, 926 KiB  
Review
Avian Pathogenic Escherichia coli (APEC) in Broiler Breeders: An Overview
by Jiddu Joseph, Li Zhang, Pratima Adhikari, Jeffrey D. Evans and Reshma Ramachandran
Pathogens 2023, 12(11), 1280; https://doi.org/10.3390/pathogens12111280 - 26 Oct 2023
Cited by 1 | Viewed by 3256
Abstract
Poultry meat is one of the major animal protein sources necessary to meet the global protein demand. Sustainability in broiler production is the key to achieving its continuous supply, and broiler breeders play a critical role in maintaining this sustainability by providing good [...] Read more.
Poultry meat is one of the major animal protein sources necessary to meet the global protein demand. Sustainability in broiler production is the key to achieving its continuous supply, and broiler breeders play a critical role in maintaining this sustainability by providing good quality chicks. Colibacillosis, the disease caused by avian pathogenic Escherichia coli (APEC), causes severe economic losses to the poultry industry globally. Moreover, APEC causes an additional burden among broiler breeders, such as a decrease in egg production and mortality among these birds. There is vertical transmission of APEC to the broiler chicks through eggs, resulting in increased first-week mortality and subsequent horizontal transmission at the hatchery. In this regard, the vertical transmission of antibiotic resistance genes is another concern that needs attention. Controlling several diseases in broiler breeders would possibly reduce the first-week mortality in chicks, thereby maintaining the production level. For that, constant monitoring of the bacterial populations is critical. Moreover, amidst the increased antibiotic resistance pattern, more focus on alternative treatment strategies like vaccines, probiotics, and bacteriophages is necessary. Future research focusing on strategies to mitigate APEC in broiler breeders would be one of the finest solutions for sustainable broiler production. Full article
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10 pages, 1807 KiB  
Article
Genetic Evaluation of Bovine Papillomavirus Types Associated with Teat Papillomatosis in Polish Dairy Cattle with the Report of a New Putative Type
by Paulina Pyrek, Michał Bednarski, Jarosław Popiel, Magdalena Siedlecka and Magdalena Karwańska
Pathogens 2023, 12(11), 1278; https://doi.org/10.3390/pathogens12111278 - 25 Oct 2023
Viewed by 1118
Abstract
Teat papillomatosis is reported to be one of the factors causing mastitis and milk losses in dairy cattle. Little is known about bovine papillomavirus (BPV) circulation in the European cattle population, and no reports can yet be found about its prevalence in Polish [...] Read more.
Teat papillomatosis is reported to be one of the factors causing mastitis and milk losses in dairy cattle. Little is known about bovine papillomavirus (BPV) circulation in the European cattle population, and no reports can yet be found about its prevalence in Polish herds. In this study, 177 BPV-like lesions were collected from teats of 109 slaughtered cows. BPV was identified in 39 of the examined animals, using PCR amplification and Sanger dideoxy sequencing. In total, 10 BPV types were isolated, among which the most common were infections caused by types 8 and 7. Macroscopically, “rice-grain” type lesions dominated (76%) and were mainly found on one teat (57.4%). The diversity of BPV types causing teat papillomatosis in Polish cows seems to be large, with nine already known types isolated and a new putative type found. The spread of new types among the worldwide cattle population can be seen for the first time, as type 25 and so called isolates BPV42 and BPV43 were found in the European cattle population. Full article
(This article belongs to the Section Viral Pathogens)
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24 pages, 1192 KiB  
Review
Salmonella Infection in Pigs: Disease, Prevalence, and a Link between Swine and Human Health
by Laura Soliani, Gianluca Rugna, Alice Prosperi, Chiara Chiapponi and Andrea Luppi
Pathogens 2023, 12(10), 1267; https://doi.org/10.3390/pathogens12101267 - 21 Oct 2023
Cited by 3 | Viewed by 2914
Abstract
Salmonella is one of the most spread foodborne pathogens worldwide, and Salmonella infections in humans still represent a global health burden. The main source of Salmonella infections in humans is represented by contaminated animal-derived foodstuffs, with pork products being one of the most [...] Read more.
Salmonella is one of the most spread foodborne pathogens worldwide, and Salmonella infections in humans still represent a global health burden. The main source of Salmonella infections in humans is represented by contaminated animal-derived foodstuffs, with pork products being one of the most important players. Salmonella infection in swine is critical not only because it is one of the main causes of economic losses in the pork industry, but also because pigs can be infected by several Salmonella serovars, potentially contaminating the pig meat production chain and thus posing a significant threat to public health globally. As of now, in Europe and in the United States, swine-related Salmonella serovars, e.g., Salmonella Typhimurium and its monophasic variant Salmonella enterica subsp. enterica 1,4,[5],12:i:-, are also frequently associated with human salmonellosis cases. Moreover, multiple outbreaks have been reported in the last few decades which were triggered by the consumption of Salmonella-contaminated pig meat. Throughout the years, changes and evolution across the pork industry may have acted as triggers for new issues and obstacles hindering Salmonella control along the food chain. Gathered evidence reinforces the importance of coordinating control measures and harmonizing monitoring programs for the efficient control of Salmonella in swine. This is necessary in order to manage outbreaks of clinical disease in pigs and also to protect pork consumers by controlling Salmonella subclinical carriage and shedding. This review provides an update on Salmonella infection in pigs, with insights on Salmonella ecology, focusing mainly on Salmonella Choleraesuis, S. Typhimurium, and S. 1,4,[5],12:i:-, and their correlation to human salmonellosis cases. An update on surveillance methods for epidemiological purposes of Salmonella infection in pigs and humans, in a “One Health” approach, will also be reported. Full article
(This article belongs to the Special Issue Swine Bacterial Pathogens from a One Health Perspective)
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12 pages, 1900 KiB  
Article
Epidemiological Characteristics of Carbapenem-Resistant Enterobacterales in Japan: A Nationwide Analysis of Data from a Clinical Laboratory Center (2016–2022)
by Kentarou Takei, Miho Ogawa, Ryuji Sakata and Hajime Kanamori
Pathogens 2023, 12(10), 1246; https://doi.org/10.3390/pathogens12101246 - 16 Oct 2023
Cited by 1 | Viewed by 1302
Abstract
In Japan, nationwide epidemiological surveys on carbapenem-resistant Enterobacterales (CREs), including comprehensive information, are scarce, with most data available only through public reports. This study analyzed data on the Enterobacterales family collected from nationwide testing centers between January 2016 and December 2022, focusing on [...] Read more.
In Japan, nationwide epidemiological surveys on carbapenem-resistant Enterobacterales (CREs), including comprehensive information, are scarce, with most data available only through public reports. This study analyzed data on the Enterobacterales family collected from nationwide testing centers between January 2016 and December 2022, focusing on isolates that met the criteria for CRE in Japan based on drug susceptibility. We investigated 5,323,875 Enterobacterales isolates of 12 different species; among 4696 (0.09%) CRE strains, the proportion of major CRE isolates was as follows: Escherichia coli, 31.3%; Klebsiella pneumoniae, 28.0%; Enterobacter cloacae, 18.5%; and Klebsiella aerogenes, 6.7%. Moreover, over a 7-year period, Providencia rettgeri, E. cloacae, K. aerogenes, and K. pneumoniae demonstrated relatively high CRE percentages of 0.6% (156/26,185), 0.47% (869/184,221), 0.28% (313/110,371), and 0.17% (1314/780,958), respectively. The number of CRE strains isolated from different samples was as follows: urine, 2390; respiratory specimens, 1254; stool, 425; blood, 252; others, 375. In the broader context, including colonization, the predominant isolates of CREs collected at nationwide testing centers are E. coli and K. pneumoniae. Furthermore, recently, attention has been directed toward less common CRE species, such as Klebsiella oxytoca and Providencia rettgeri, and thus, it might be necessary to continue monitoring these less common species. Full article
(This article belongs to the Special Issue Detection and Epidemiology of Drug-Resistant Bacteria)
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15 pages, 1636 KiB  
Article
Characterization of mRNA Signature in Milk Small Extracellular Vesicles from Cattle Infected with Bovine Leukemia Virus
by Md. Matiur Rahman, Hinata Ishikawa, Marika Yamauchi, Shigeo Takashima, Yuji O. Kamatari, Kaori Shimizu, Ayaka Okada and Yasuo Inoshima
Pathogens 2023, 12(10), 1239; https://doi.org/10.3390/pathogens12101239 - 13 Oct 2023
Cited by 1 | Viewed by 2280
Abstract
This study aimed to characterize the mRNA signature of milk small extracellular vesicles (sEVs) from BLV-infected cattle. A total of 23 mRNAs, which showed greater abundance in milk sEVs from BLV-infected cattle compared to those from BLV-uninfected (control) cattle, were identified through microarray [...] Read more.
This study aimed to characterize the mRNA signature of milk small extracellular vesicles (sEVs) from BLV-infected cattle. A total of 23 mRNAs, which showed greater abundance in milk sEVs from BLV-infected cattle compared to those from BLV-uninfected (control) cattle, were identified through microarray analyses conducted in our previous study. To assess the significance of these differences in mRNA abundance, milk was collected from six control cattle and twenty-six cattle infected with BLV. The infected cattle were categorized into two distinct groups based on their proviral loads: a group of eight cattle with low proviral loads (LPVL), characterized by <10,000 copies per 105 white blood cells (WBC), and a group of eighteen cattle with high proviral loads (HPVL), marked by ≥10,000 copies per 105 WBC. The qPCR analysis quantified 7 out of 23 mRNAs, including BoLA, CALB1, IL33, ITGB2, MYOF, TGFBR1, and TMEM156, in the milk sEVs from control cattle, LPVL cattle, and HPVL cattle. Significantly, the average relative expression of CALB1 mRNA in milk sEVs was higher in LPVL cattle compared to HPVL cattle and control cattle (p < 0.05), while it was relatively lower in HPVL cattle compared to LPVL cattle and control cattle (p > 0.05). Likewise, the average relative expression of TMEM156 mRNA in milk sEVs was significantly higher in LPVL cattle compared to HPVL cattle (p < 0.05), and relatively lower in HPVL cattle compared to LPVL cattle and control cattle (p > 0.05). The results indicate distinct patterns of CALB1 and TMEM156 mRNA levels in milk sEVs, with higher levels observed in LPVL cattle and lower levels in HPVL cattle. The current study could provide essential information to comprehend the complexities during the progression of BLV infection and direct the exploration of mRNA biomarkers for monitoring the clinical stage of BLV infection. Full article
(This article belongs to the Special Issue Diagnostics of Animal Viral Infectious Diseases)
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13 pages, 1804 KiB  
Article
Human Papillomavirus Genotype Richness and the Biodiversity of Squamous and Glandular Cervical Dysplasias: A Cross-Sectional Study
by Elisa Gozzini, Davide Radice, Fabio Bottari, Sara Boveri, Maria Elena Guerrieri, Eleonora Petra Preti, Noemi Spolti, Mariacristina Ghioni, Federico Ferrari and Anna Daniela Iacobone
Pathogens 2023, 12(10), 1234; https://doi.org/10.3390/pathogens12101234 - 11 Oct 2023
Viewed by 2596
Abstract
The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of [...] Read more.
The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson’s biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age (p = 0.007) and histologic grade (p < 0.001). Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers. Full article
(This article belongs to the Special Issue Epidemiology of Human Papillomavirus Infection)
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17 pages, 11271 KiB  
Article
In Vivo Efficacy of Curcumin and Curcumin Nanoparticle in Trypanosoma congolense, Broden 1904 (Kinetoplastea: Trypanosomatidae)-Infected Mice
by Nthatisi Innocentia Molefe-Nyembe, Oluyomi Stephen Adeyemi, Daisuke Kondoh, Kentaro Kato, Noboru Inoue and Keisuke Suganuma
Pathogens 2023, 12(10), 1227; https://doi.org/10.3390/pathogens12101227 - 09 Oct 2023
Viewed by 1115
Abstract
Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. [...] Read more.
Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. b. brucei, and T. evansi. Additionally, CUR and CUR-nanoparticle anti-Trypanosoma efficacy were assessed in vivo against T. congolense. All the CUR-nanoparticles were two folds more effective on the T. congolense as compared to CUR in vitro, with recorded efficacy of 3.67 ± 0.31; 7.61 ± 1.22; and 6.40 ± 3.07 μM, while the CUR-nanoparticles efficacy was 1.56 ± 0.50; 28.16 ± 9.43 and 13.12 ± 0.13 μM on T. congolense, T. b. brucei, and T. evansi, respectively. Both CUR and CUR-nanoparticles displayed moderate efficacy orally. The efficacy of CUR and CUR-nanoparticles in vivo was influenced by solubility, presence of food, and treatment period. CUR-treated mice were not cured of the infection; however, the survival rate of the orally treated mice was significantly prolonged as compared with intraperitoneal-treated mice. CUR-nanoparticles resulted in significant suppression of parasitemia even though relapsed was observed. In conclusion, CUR and CUR-nanoparticles possess moderate efficacy orally on the trypanosomes as compared to the intraperitoneal treatment. Full article
(This article belongs to the Special Issue Parasitic Infections and Diseases of Domestic Animals)
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15 pages, 5891 KiB  
Review
An Update on the Current State of SARS-CoV-2 Mac1 Inhibitors
by Joseph J. O’Connor, Dana Ferraris and Anthony R. Fehr
Pathogens 2023, 12(10), 1221; https://doi.org/10.3390/pathogens12101221 - 07 Oct 2023
Viewed by 1253
Abstract
Non-structural protein 3 (nsp3) from all coronaviruses (CoVs) contains a conserved macrodomain, known as Mac1, that has been proposed as a potential therapeutic target for CoVs due to its critical role in viral pathogenesis. Mac1 is an ADP-ribose binding protein and ADP-ribosylhydrolase that [...] Read more.
Non-structural protein 3 (nsp3) from all coronaviruses (CoVs) contains a conserved macrodomain, known as Mac1, that has been proposed as a potential therapeutic target for CoVs due to its critical role in viral pathogenesis. Mac1 is an ADP-ribose binding protein and ADP-ribosylhydrolase that promotes replication and blocks IFN responses, though the precise mechanisms it uses to carry out these functions remain unknown. Over the past 3 years following the onset of COVID-19, several groups have used high-throughput screening with multiple assays and chemical modifications to create unique chemical inhibitors of the SARS-CoV-2 Mac1 protein. Here, we summarize the current efforts to identify selective and potent inhibitors of SARS-CoV-2 Mac1. Full article
(This article belongs to the Special Issue ADP-Ribosylation in Pathogens)
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11 pages, 439 KiB  
Article
Neurocysticercosis Diagnosis in a Non-Endemic Country: France
by Ines Zemmour, Marie-Fleur Durieux, Etienne Herault, Célia Rouges, Barbara Šoba, Aurélien Mercier, Frédéric Ariey, Pierre-Marie Preux, Hélène Yera and on behalf of Collaborators Group
Pathogens 2023, 12(10), 1205; https://doi.org/10.3390/pathogens12101205 - 29 Sep 2023
Viewed by 1009
Abstract
Diagnosing neurocysticercosis (NCC) is difficult due to its variable clinical presentations and the different imaging techniques used to detect brain damage. This study aimed to evaluate the use of cerebrospinal fluid serology and PCR for diagnosing biological neurocysticercosis in a non-endemic country. We [...] Read more.
Diagnosing neurocysticercosis (NCC) is difficult due to its variable clinical presentations and the different imaging techniques used to detect brain damage. This study aimed to evaluate the use of cerebrospinal fluid serology and PCR for diagnosing biological neurocysticercosis in a non-endemic country. We tested samples from patients living in France with suspected NCC and confirmed that 45 of the patients presented with the disease. A total of 89% of patients had previously traveled to countries where the disease was endemic. The sensitivity of Western blots compared to ELISA was not significantly different (80% vs. 60%) (p > 0.05), and neither was the sensitivity of Western blots vs. PCR (78% vs. 56%) (p > 0.05). The PCR sensitivity was 78% and 47% in definitive NCC and in probable NCC. PCR tests using cerebrospinal fluid should be considered as a diagnostic criterion for identifying NCC. Full article
(This article belongs to the Special Issue Recent Advances in Taeniasis and Cysticercosis)
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34 pages, 2450 KiB  
Review
The In Vitro Antimicrobial Susceptibility of Borrelia burgdorferi sensu lato: Shedding Light on the Known Unknowns
by Klaus-Peter Hunfeld, Peter Kraiczy, Douglas E. Norris and Benedikt Lohr
Pathogens 2023, 12(10), 1204; https://doi.org/10.3390/pathogens12101204 - 28 Sep 2023
Viewed by 1941
Abstract
Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most [...] Read more.
Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most important human tick-borne illness in the Northern Hemisphere. The causative agent was identified and successfully isolated in 1982 and, shortly thereafter, antibiotic treatment was found to be safe and efficacious. Since then, various in vitro studies have been conducted in order to improve our knowledge of the activity of antimicrobial agents against B. burgdorferi s. l. The full spectrum of in vitro antibiotic susceptibility has still not been defined for some of the more recently developed compounds. Moreover, our current understanding of the in vitro interactions between B. burgdorferi s. l. and antimicrobial agents, and their possible mechanisms of resistance remains very limited and is largely based on in vitro susceptibility experiments on only a few isolates of Borrelia. Even less is known about the possible mechanisms of the in vitro persistence of spirochetes exposed to antimicrobial agents in the presence of human and animal cell lines. Only a relatively small number of laboratory studies and cell culture experiments have been conducted. This review summarizes what is and what is not known about the in vitro susceptibility of B. burgdorferi s. l. It aims to shed light on the known unknowns that continue to fuel current debates on possible treatment resistance and mechanisms of persistence of Lyme disease spirochetes in the presence of antimicrobial agents. Full article
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14 pages, 995 KiB  
Review
Epidemiology and Transmission of Theileria orientalis in Australasia
by Biniam T. Lakew, Steve Eastwood and Stephen W. Walkden-Brown
Pathogens 2023, 12(10), 1187; https://doi.org/10.3390/pathogens12101187 - 22 Sep 2023
Cited by 2 | Viewed by 1143
Abstract
Oriental theileriosis, a disease primarily impacting cattle is caused by an apicomplexan hemoprotozoan parasite, Theileria orientalis. It has now become established in the Australasia region. The organism was long considered a benign cause of persistent infections; however, an increase in clinical outbreaks [...] Read more.
Oriental theileriosis, a disease primarily impacting cattle is caused by an apicomplexan hemoprotozoan parasite, Theileria orientalis. It has now become established in the Australasia region. The organism was long considered a benign cause of persistent infections; however, an increase in clinical outbreaks since 2006 in the eastern Australian states and New Zealand was associated with the identification of the pathogenic Ikeda (Type 2) and Chitose (Type 1) genotypes. Unlike the pathogenic T. parva and T. annulate, which target leucocytes, clinical manifestation with T. orientalis is due to its effects on erythrocytes, with the infection sometimes designated as Theileria associated bovine anemia (TABA). In Australia and New Zealand, the tick Haemaphysalis longicornis is the principal vector, though other Haemaphysalis species are also likely vectors. The endemic status of infection with pathogenic genotypes in areas with low or absent tick populations is an apparent paradox that may be attributable to alternative modes of transmission, such as mechanical transmission by hematophagous insects (lice, mosquitoes, and biting flies), vertical transmission, and transmission via iatrogenic means. This review addresses the evidence for the different modes of transmission of T. orientalis with particular focus on the reported and potential vectors in Australasia. Full article
(This article belongs to the Special Issue Bovine Theileriosis Caused by the Theileria orientalis Group)
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20 pages, 2371 KiB  
Review
Rift Valley Fever Virus—Infection, Pathogenesis and Host Immune Responses
by Niranjana Nair, Albert D. M. E. Osterhaus, Guus F. Rimmelzwaan and Chittappen Kandiyil Prajeeth
Pathogens 2023, 12(9), 1174; https://doi.org/10.3390/pathogens12091174 - 19 Sep 2023
Cited by 6 | Viewed by 2265
Abstract
Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate [...] Read more.
Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate proinflammatory immune responses and lead to attenuation of the virus. Upon infection, virus-specific antibodies and T cells are induced that may afford protection against subsequent infections. Thus, all arms of the adaptive immune system contribute to prevention of disease progression. These findings will aid the design of vaccines using the currently available platforms. Vaccine candidates have shown promise in safety and efficacy trials in susceptible animal species and these may contribute to the control of RVFV infections and prevention of disease progression in humans and ruminants. Full article
(This article belongs to the Special Issue Current Advances in Flavivirus and Other Arboviruses)
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14 pages, 2418 KiB  
Article
Interferon-λ Activates a Differential Response in Peripheral Neurons That Is Effective against Alpha Herpesvirus Infections
by Stephanie Salazar, Khanh T. Y. Luong, Taulima Nua and Orkide O. Koyuncu
Pathogens 2023, 12(9), 1142; https://doi.org/10.3390/pathogens12091142 - 07 Sep 2023
Cited by 3 | Viewed by 1429
Abstract
Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is [...] Read more.
Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is not well understood. Using primary neurons cultured in compartmentalized chambers, prior studies performed on Pseudorabies virus (PRV) have demonstrated that type I and type II interferons (IFNs) induce a local antiviral response in axons via distinct mechanisms leading to a reduction in viral particle transport to the neuronal nucleus. A new class of interferons known as type III IFNs has been shown to play an immediate role against viral infection in mucosal epithelial cells. However, the antiviral effects of type III IFNs within neurons during α-HV infection are largely unknown. In this study, we focused on elucidating the antiviral activity of type III IFN against PRV neuronal infection, and we compared the interferon-stimulated gene (ISGs) induction pattern in neurons to non-neuronal cells. We found that IFN pre-exposure of both primary neurons and fibroblast cells significantly reduces PRV virus yield, albeit by differential STAT activation and ISG induction patterns. Notably, we observed that type III IFNs trigger the expression of a subset of ISGs mainly through STAT1 activation to induce an antiviral state in primary peripheral neurons. Full article
(This article belongs to the Special Issue Host–Virus Interactions in the Nervous System)
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20 pages, 4370 KiB  
Article
Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi
by Danielle Pessôa-Pereira, Breanna M. Scorza, Karen I. Cyndari, Erin A. Beasley and Christine A. Petersen
Pathogens 2023, 12(9), 1128; https://doi.org/10.3390/pathogens12091128 - 04 Sep 2023
Viewed by 1883
Abstract
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, [...] Read more.
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs. Full article
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20 pages, 1408 KiB  
Review
Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus
by Federica Attaianese, Sara Guiducci, Sandra Trapani, Federica Barbati, Lorenzo Lodi, Giuseppe Indolfi, Chiara Azzari and Silvia Ricci
Pathogens 2023, 12(9), 1118; https://doi.org/10.3390/pathogens12091118 - 01 Sep 2023
Cited by 2 | Viewed by 1631
Abstract
Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and [...] Read more.
Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and adaptive immune components involved, including the recognition of RSV, the inflammatory response, the role of natural killer (NK) cells, antigen presentation, T cell response, and antibody production. Understanding the complex immune response to hRSV infection is crucial for developing effective interventions against this significant respiratory pathogen. Further investigations into the immune memory generated by hRSV infection and the development of strategies to enhance immune responses may hold promise for the prevention and management of hRSV-associated diseases. Full article
(This article belongs to the Special Issue Immunity to Respiratory Infections)
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14 pages, 9317 KiB  
Article
Effects of Host Plants and Their Infection Status on Acquisition and Inoculation of A Plant Virus by Its Hemipteran Vector
by Saurabh Gautam, Kiran R. Gadhave, James W. Buck, Bhabesh Dutta, Timothy Coolong, Scott Adkins, Alvin M. Simmons and Rajagopalbabu Srinivasan
Pathogens 2023, 12(9), 1119; https://doi.org/10.3390/pathogens12091119 - 01 Sep 2023
Cited by 1 | Viewed by 1166
Abstract
Whitefly, Bemisia tabaci Gennadius (B cryptic species), transmits cucurbit leaf crumple virus (CuLCrV) in a persistent fashion. CuLCrV affects several crops such as squash and snap bean in the southeastern United States. CuLCrV is often found as a mixed infection with whitefly transmitted [...] Read more.
Whitefly, Bemisia tabaci Gennadius (B cryptic species), transmits cucurbit leaf crumple virus (CuLCrV) in a persistent fashion. CuLCrV affects several crops such as squash and snap bean in the southeastern United States. CuLCrV is often found as a mixed infection with whitefly transmitted criniviruses, such as cucurbit yellow stunting disorder virus (CYSDV) in hosts such as squash, or as a single infection in hosts such as snap bean. The implications of different host plants (inoculum sources) with varying infection status on CuLCrV transmission/epidemics is not clear. This study conducted a series of whitefly mediated CuLCrV transmission experiments. In the first experiment, three plants species: squash, snap bean, and tobacco were inoculated by whiteflies feeding on field-collected mixed-infected squash plants. In the second experiment, three plant species, namely squash, snap bean, and tobacco with varying infection status (squash infected with CuLCrV and CYSDV and snap bean and tobacco infected with CuLCrV), were used as inoculum sources. In the third experiment, squash plants with differential CuLCrV accumulation levels and infection status (either singly infected with CuLCrV or mixed infected with CuLCrV and CYSDV) were used as inoculum sources. Irrespective of plant species and its infection status, CuLCrV accumulation in whiteflies was dependent upon the CuLCrV accumulation in the inoculum source plants. Furthermore, differential CuLCrV accumulation in whiteflies resulted in differential transmission, CuLCrV accumulation, and disease phenotype in the recipient squash plants. Overall, results demonstrate that whitefly mediated CuLCrV transmission between host plants follows a virus density dependent phenomenon with implications for epidemics. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)
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22 pages, 3012 KiB  
Article
Mycobacterium tuberculosis Central Metabolism Is Key Regulator of Macrophage Pyroptosis and Host Immunity
by Michelle E. Maxson, Lahari Das, Michael F. Goldberg, Steven A. Porcelli, John Chan and William R. Jacobs, Jr.
Pathogens 2023, 12(9), 1109; https://doi.org/10.3390/pathogens12091109 - 30 Aug 2023
Cited by 1 | Viewed by 1839
Abstract
Metabolic dysregulation in Mycobacterium tuberculosis results in increased macrophage apoptosis or pyroptosis. However, mechanistic links between Mycobacterium virulence and bacterial metabolic plasticity remain ill defined. In this study, we screened random transposon insertions of M. bovis BCG to identify mutants that induce pyroptotic [...] Read more.
Metabolic dysregulation in Mycobacterium tuberculosis results in increased macrophage apoptosis or pyroptosis. However, mechanistic links between Mycobacterium virulence and bacterial metabolic plasticity remain ill defined. In this study, we screened random transposon insertions of M. bovis BCG to identify mutants that induce pyroptotic death of the infected macrophage. Analysis of the transposon insertion sites identified a panel of fdr (functioning death repressor) genes, which were shown in some cases to encode functions central to Mycobacterium metabolism. In-depth studies of one fdr gene, fdr8 (BCG3787/Rv3727), demonstrated its important role in the maintenance of M. tuberculosis and M. bovis BCG redox balance in reductive stress conditions in the host. Our studies expand the subset of known Mycobacterium genes linking bacterial metabolic plasticity to virulence and also reveal that the broad induction of pyroptosis by an intracellular bacterial pathogen is linked to enhanced cellular immunity in vivo. Full article
(This article belongs to the Special Issue Biology of Mycobacterial Pathogens)
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16 pages, 2793 KiB  
Article
Evaluation of a Tetracycline-Resistant E. coli Enumeration Method for Correctly Classifying E. coli in Environmental Waters in Kentucky, USA
by Callie Boggs, Kidus Shiferawe, Eckhardt Karsten, Jayden Hamlet, S. Travis Altheide and Jason W. Marion
Pathogens 2023, 12(9), 1090; https://doi.org/10.3390/pathogens12091090 - 28 Aug 2023
Viewed by 1415
Abstract
The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. [...] Read more.
The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. coli, are common agents linked to AMR-related deaths (23% of cases). Culture-based methods for detecting tetracycline-resistant E. coli may be of practical value for AMR monitoring in limited resource environments. This study evaluated the ColiGlow™ method with tetracycline for classifying tetracycline-resistant E. coli. A total of 61 surface water samples from Kentucky, USA (2020–2022), provided 61 presumed E. coli isolates, of which 28 isolates were obtained from tetracycline-treated media. Species identification and tetracycline resistance evaluation were performed. It was found that 82% of isolates were E. coli, and 18% were other species; 97% were identified as E. coli when using the API20E identification system. The MicroScan system yielded Enterobacter cloacae false positives in 20% of isolates. Adding tetracycline to ColiGlow increased the odds of isolating tetracycline-resistant E. coli 18-fold. Tetracycline-treated samples yielded 100% tetracycline-resistant E. coli when the total E. coli densities were within the enumeration range of the method. ColiGlow with tetracycline shows promise for monitoring tetracycline-resistant E. coli in natural waters and potentially aiding AMR surveillance in resource-limited settings among other environments. Full article
(This article belongs to the Special Issue Water-Borne Pathogens)
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17 pages, 9957 KiB  
Article
Evaluation of Wild Peanut Species and Their Allotetraploids for Resistance against Thrips and Thrips-Transmitted Tomato Spotted Wilt Orthotospovirus (TSWV)
by Yi-Ju Chen, Sudeep Pandey, Michael Catto, Soraya Leal-Bertioli, Mark R. Abney, Sudeep Bag, Mark Hopkins, Albert Culbreath and Rajagopalbabu Srinivasan
Pathogens 2023, 12(9), 1102; https://doi.org/10.3390/pathogens12091102 - 28 Aug 2023
Cited by 2 | Viewed by 1395
Abstract
Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis [...] Read more.
Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis species can serve as important sources of resistance, and despite ploidy barriers (cultivated peanut is tetraploid), their usage in breeding programs is now possible because of the knowledge and development of induced interspecific allotetraploid hybrids. This study screened 10 wild diploid Arachis and six induced allotetraploid genotypes via thrips-mediated TSWV transmission assays and thrips’ feeding assays in the greenhouse. Three parameters were evaluated: percent TSWV infection, virus accumulation, and temporal severity of thrips feeding injury. Results indicated that the diploid A. stenosperma accession V10309 and its derivative-induced allotetraploid ValSten1 had the lowest TSWV infection incidences among the evaluated genotypes. Allotetraploid BatDur1 had the lowest thrips-inflicted damage at each week post thrips release, while diploid A. batizocoi accession K9484 and A. duranensis accession V14167 had reduced feeding damage one week post thrips release, and diploids A. valida accession GK30011 and A. batizocoi had reduced feeding damage three weeks post thrips releasethan the others. Overall, plausible TSWV resistance in diploid species and their allotetraploid hybrids was characterized by reduced percent TSWV infection, virus accumulation, and feeding severity. Furthermore, a few diploids and tetraploid hybrids displayed antibiosis against thrips. These results document evidence for resistance against TSWV and thrips in wild diploid Arachis species and peanut-compatible-induced allotetraploids. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)
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14 pages, 675 KiB  
Review
Joining Forces against Antibiotic Resistance: The One Health Solution
by Eleonora Cella, Marta Giovanetti, Francesca Benedetti, Fabio Scarpa, Catherine Johnston, Alessandra Borsetti, Giancarlo Ceccarelli, Taj Azarian, Davide Zella and Massimo Ciccozzi
Pathogens 2023, 12(9), 1074; https://doi.org/10.3390/pathogens12091074 - 23 Aug 2023
Cited by 12 | Viewed by 2841
Abstract
Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle [...] Read more.
Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle complex health challenges such as antibiotic resistance. In the context of One Health, antibiotic resistance refers to the ability of bacteria to withstand the efficacy of antibiotics, rendering them less effective or completely ineffective in treating infections. The emergence and spread of antibiotic-resistant bacteria pose a threat to human and animal health, as well as to the effectiveness of medical treatments and veterinary interventions. In particular, One Health recognizes that antibiotic use in human medicine, animal agriculture, and the environment are interconnected factors contributing to the development and spread of antibiotic resistance. For example, the misuse and overuse of antibiotics in human healthcare, including inappropriate prescribing and patient non-compliance, can contribute to the selection and spread of resistant bacteria. Similarly, the use of antibiotics in livestock production for growth promotion and disease prevention can contribute to the development of antibiotic resistance in animals and subsequent transmission to humans through the food chain. Addressing antibiotic resistance requires a collaborative One Health approach that involves multiple participants, including healthcare professionals, veterinarians, researchers, and policymakers. Full article
(This article belongs to the Special Issue Reviews of Infectious Diseases)
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18 pages, 16402 KiB  
Article
Genomic and Phylogenetic Analysis of Bacillus cereus Biovar anthracis Isolated from Archival Bone Samples Reveals Earlier Natural History of the Pathogen
by Michael H. Norris, Diansy Zincke, David J. Daegling, John Krigbaum, W. Scott McGraw, Alexander Kirpich, Ted L. Hadfield and Jason K. Blackburn
Pathogens 2023, 12(8), 1065; https://doi.org/10.3390/pathogens12081065 - 20 Aug 2023
Viewed by 1366
Abstract
(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic [...] Read more.
(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic analysis found that B. cereus had acquired two anthrax-like plasmids, one a pXO1-like toxin producing plasmid and the other a pXO2-like plasmid encoding capsule. Bcbva caused animal fatalities in Cameroon, Democratic Republic of Congo, and the Central African Republic between 2004 and 2012. (2) Methods: The pathogen had acquired plasmids in the wild and that was discovered as the cause of widespread animal fatalities in the early 2000s. Primate bones had been shipped out of the endemic zone for anthropological studies prior to the realized danger of contamination with Bcbva. Spores were isolated from the bone fragments and positively identified as Bcbva. Strains were characterized by classical microbiological methods and qPCR. Four new Bcbva isolates were whole-genome sequenced. Chromosomal and plasmid phylogenomic analysis was performed to provide temporal and spatial context to these new strains and previously sequenced Bcbva. Tau and principal component analyses were utilized to identify genetic and spatial case patterns in the Taï National Park anthrax zone. (3) Results: Preliminary studies positively identified Bcbva presence in several archival bone fragments. The animals in question died between 1994 and 2010. Previously, the earliest archival strains of Bcbva were identified in 1996. Though the pathogen has a homogeneous genome, spatial analyses of a subset of mappable isolates from Taï National Park revealed strains found closer together were generally more similar, with strains from chimpanzees and duikers having the widest distribution. Ancestral strains were located mostly in the west of the park and had lower spatial clustering compared to more recent isolates, indicating a local increase in genetic diversity of Bcbva in the park over space and time. Global clustering analysis indicates patterns of genetic diversity and distance are shared between the ancestral and more recently isolated type strains. (4) Conclusions: Our strains have the potential to unveil historical genomic information not available elsewhere. This information sheds light on the evolution and emergence of a dangerous anthrax-causing pathogen. Full article
(This article belongs to the Special Issue Anthrax—a Threat beyond Bacillus anthracis)
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19 pages, 2303 KiB  
Review
Malaria Genomics, Vaccine Development, and Microbiome
by Xinzhuan Su, Rachel V. Stadler, Fangzheng Xu and Jian Wu
Pathogens 2023, 12(8), 1061; https://doi.org/10.3390/pathogens12081061 - 18 Aug 2023
Viewed by 1920
Abstract
Recent advances in malaria genetics and genomics have transformed many aspects of malaria research in areas of molecular evolution, epidemiology, transmission, host–parasite interaction, drug resistance, pathogenicity, and vaccine development. Here, in addition to introducing some background information on malaria parasite biology, parasite genetics/genomics, [...] Read more.
Recent advances in malaria genetics and genomics have transformed many aspects of malaria research in areas of molecular evolution, epidemiology, transmission, host–parasite interaction, drug resistance, pathogenicity, and vaccine development. Here, in addition to introducing some background information on malaria parasite biology, parasite genetics/genomics, and genotyping methods, we discuss some applications of genetic and genomic approaches in vaccine development and in studying interactions with microbiota. Genetic and genomic data can be used to search for novel vaccine targets, design an effective vaccine strategy, identify protective antigens in a whole-organism vaccine, and evaluate the efficacy of a vaccine. Microbiota has been shown to influence disease outcomes and vaccine efficacy; studying the effects of microbiota in pathogenicity and immunity may provide information for disease control. Malaria genetics and genomics will continue to contribute greatly to many fields of malaria research. Full article
(This article belongs to the Special Issue Models in Parasite and Pathogen Evolution)
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14 pages, 1303 KiB  
Article
Biologically Relevant Murine Models of Chronic Pseudomonas aeruginosa Respiratory Infection
by Aoife M. Rodgers, Jaime Lindsay, Avril Monahan, Alice V. Dubois, Aduragbemi A. Faniyi, Barry J. Plant, Marcus A. Mall, Miquel B. Ekkelenkamp, Stuart Elborn and Rebecca J. Ingram
Pathogens 2023, 12(8), 1053; https://doi.org/10.3390/pathogens12081053 - 17 Aug 2023
Cited by 1 | Viewed by 1437
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have [...] Read more.
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described: a clinical isolate infection model, utilising isolates obtained from patients with CF; an incomplete antibiotic clearance model, leading to bacterial bounce-back; and the establishment of chronic infection; and an adapted water bottle chronic infection model. These models circumvent the requirement for a surgical procedure and, importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease-2nd Volume)
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13 pages, 710 KiB  
Article
Presence of Equine and Bovine Coronaviruses, Endoparasites, and Bacteria in Fecal Samples of Horses with Colic
by Moritz Stummer, Vicky Frisch, Frauke Glitz, Barbara Hinney, Joachim Spergser, Jürgen Krücken, Irina Diekmann, Katharina Dimmel, Christiane Riedel, Jessika-Maximiliane V. Cavalleri, Till Rümenapf, Anja Joachim, Manolis Lyrakis and Angelika Auer
Pathogens 2023, 12(8), 1043; https://doi.org/10.3390/pathogens12081043 - 15 Aug 2023
Viewed by 1306
Abstract
Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the [...] Read more.
Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the frequency of otherwise undetected ECoV infections in horses with acute colic, fresh fecal samples of 105 horses with acute colic and 36 healthy control horses were screened for viruses belonging to the Betacoronavirus 1 species by RT-PCR as well as for gastrointestinal helminths and bacteria commonly associated with colic. Horses with colic excreted significantly fewer strongyle eggs than horses without colic. The prevalence of anaerobic, spore-forming, gram-positive bacteria (Clostridium perfringens and Clostridioides difficile) was significantly higher in the feces of horses with colic. Six horses with colic (5.7%) and one horse from the control group (2.8%) tested positive for Betacoronaviruses. Coronavirus-positive samples were sequenced to classify the virus by molecular phylogeny (N gene). Interestingly, in three out of six coronavirus-positive horses with colic, sequences closely related to bovine coronaviruses (BCoV) were found. The pathogenic potential of BCoV in horses remains unclear and warrants further investigation. Full article
(This article belongs to the Special Issue Coronaviruses: Virology and Zoonotic Potential)
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23 pages, 3241 KiB  
Article
Brucella ceti Infection in Striped Dolphins from Italian Seas: Associated Lesions and Epidemiological Data
by Carla Grattarola, Antonio Petrella, Giuseppe Lucifora, Gabriella Di Francesco, Fabio Di Nocera, Antonio Pintore, Cristiano Cocumelli, Giuliana Terracciano, Antonio Battisti, Ludovica Di Renzo, Donatella Farina, Cristina Esmeralda Di Francesco, Maria Ines Crescio, Simona Zoppi, Alessandro Dondo, Barbara Iulini, Katia Varello, Walter Mignone, Maria Goria, Virginia Mattioda, Federica Giorda, Giovanni Di Guardo, Anna Janowicz, Manuela Tittarelli, Fabrizio De Massis, Cristina Casalone and Giuliano Garofoloadd Show full author list remove Hide full author list
Pathogens 2023, 12(8), 1034; https://doi.org/10.3390/pathogens12081034 - 13 Aug 2023
Cited by 2 | Viewed by 2382
Abstract
Brucella ceti infections have been increasingly reported in cetaceans. In this study, we analyzed all cases of B. ceti infection detected in striped dolphins stranded along the Italian coastline between 2012 and 2021 (N = 24). We focused on the pathogenic role [...] Read more.
Brucella ceti infections have been increasingly reported in cetaceans. In this study, we analyzed all cases of B. ceti infection detected in striped dolphins stranded along the Italian coastline between 2012 and 2021 (N = 24). We focused on the pathogenic role of B. ceti through detailed pathological studies, and ad hoc microbiological, biomolecular, and serological investigations, coupled with a comparative genomic analysis of the strains. Neurobrucellosis was observed in 20 animals. The primary histopathologic features included non-suppurative meningoencephalitis (N = 9), meningitis (N = 6), and meningoencephalomyelitis (N = 5), which was also associated with typical lesions in other tissues (N = 8). Co-infections were detected in more than half of the cases, mostly involving Cetacean Morbillivirus (CeMV). The 24 B. ceti isolates were assigned primarily to sequence type 26 (ST26) (N = 21) and, in a few cases, ST49 (N = 3). The multilocus sequence typing (cgMLST) based on whole genome sequencing (WGS) data showed that strains from Italy clustered into four genetically distinct clades. Plotting these clades onto a geographic map suggests a link between their phylogeny and the topographical distribution. These results support the role of B. ceti as a primary neurotropic pathogen for striped dolphins and highlight the utility of WGS data in understanding the evolution of this emerging pathogen. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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16 pages, 2308 KiB  
Article
HLA-II-Dependent Neuroimmune Changes in Group A Streptococcal Necrotizing Fasciitis
by Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs and Suba Nookala
Pathogens 2023, 12(8), 1000; https://doi.org/10.3390/pathogens12081000 - 31 Jul 2023
Cited by 1 | Viewed by 1746
Abstract
Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis [...] Read more.
Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against peripheral GAS infections, these interactions may simultaneously trigger neuropathology and, in some cases, induce persistent alterations in the glial phenotypes. Here, we studied the consequences of peripheral GAS skin infection on the brain in an HLA-II transgenic mouse model of GAS NF with and without treatment with an antibiotic, clindamycin (CLN). Mice expressing the human HLA-II DR3 (DR3) or the HLA-II DR4 (DR4) allele were divided into three groups: (i) uninfected controls, (ii) subcutaneously infected with a clinical GAS strain isolated from a patient with GAS NF, and (iii) GAS-infected with CLN treatment (10 mg/kg/5 days, intraperitoneal). The groups were monitored for 15 days post-infection. Skin GAS burden and lesion area, splenic and hippocampal mRNA levels of inflammatory markers, and immunohistochemical changes in hippocampal GFAP and Iba-1 immunoreactivity were assessed. Skin GAS burden and hippocampal mRNA levels of the inflammatory markers S100A8/A9, IL-1β, IL-33, inflammasome-related caspase-1 (Casp1), and NLRP6 were elevated in infected DR3 but not DR4 mice. The levels of these markers were significantly reduced following CLN treatment in DR3 mice. Although GAS was not detectable in the brain, astrocyte (GFAP) and microglia (Iba-1) activation were evident from increased GFAP and Iba-1 mRNA levels in DR3 and DR4 mice. However, CLN treatment significantly reduced GFAP mRNA levels in DR3 mice, not DR4 mice. Our data suggest a skin–brain axis during GAS NF, demonstrating that peripherally induced pathological conditions regulate neuroimmune changes and gliotic events in the brain. Full article
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14 pages, 1528 KiB  
Article
Dynamics of Infections in Cattle and Rhipicephalus microplus: A Preliminary Study
by Elianne Piloto-Sardiñas, Angélique Foucault-Simonin, Alejandra Wu-Chuang, Lourdes Mateos-Hernández, Roxana Marrero-Perera, Lianet Abuin-Denis, Lisset Roblejo-Arias, Cristian Díaz-Corona, Zbigniew Zając, Joanna Kulisz, Aneta Woźniak, Sara Moutailler, Belkis Corona-González and Alejandro Cabezas-Cruz
Pathogens 2023, 12(8), 998; https://doi.org/10.3390/pathogens12080998 - 30 Jul 2023
Cited by 2 | Viewed by 1336
Abstract
Tick-borne pathogens (TBPs) pose a significant threat to livestock, including bovine species. This study aimed to investigate TBPs in cattle and ticks across four sampling points, utilizing real-time microfluidic PCR. The results revealed that Rhipicephalus microplus ticks were found infesting all animals. Among [...] Read more.
Tick-borne pathogens (TBPs) pose a significant threat to livestock, including bovine species. This study aimed to investigate TBPs in cattle and ticks across four sampling points, utilizing real-time microfluidic PCR. The results revealed that Rhipicephalus microplus ticks were found infesting all animals. Among the detected TBPs in cattle, Anaplasma marginale was the most frequently identified, often as a single infection, although mixed infections involving Rickettsia felis, uncharacterized Rickettsia sp., and Anaplasma sp. were also observed. In ticks, A. marginale was predominant, along with R. felis, Rickettsia sp., and Ehrlichia sp. It is noteworthy that although A. marginale consistently infected all cattle during various sampling times, this pathogen was not detected in all ticks. This suggests a complex dynamic of pathogen acquisition by ticks. A phylogenetic analysis focused on the identification of Anaplasma species using amplified 16S rDNA gene fragments revealed the presence of A. marginale and Anaplasma platys strains in bovines. These findings underscore the presence of multiple TBPs in both cattle and ticks, with A. marginale being the most prevalent. Understanding the dynamics and phylogenetics of TBPs is crucial for developing effective control strategies to mitigate tick-borne diseases in livestock. Full article
(This article belongs to the Collection Advances in Tick Research)
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14 pages, 3549 KiB  
Article
Genomic Analysis of Yersinia pestis Strains from Brazil: Search for Virulence Factors and Association with Epidemiological Data
by João Luiz de Lemos Padilha Pitta, Matheus Filgueira Bezerra, Diego Leandro Reis da Silva Fernandes, Tessa de Block, Ane de Souza Novaes, Alzira Maria Paiva de Almeida and Antonio Mauro Rezende
Pathogens 2023, 12(8), 991; https://doi.org/10.3390/pathogens12080991 - 28 Jul 2023
Viewed by 1425
Abstract
Yersinia pestis, the etiological agent of the plague, is considered a genetically homogeneous species. Brazil is currently in a period of epidemiological silence but plague antibodies are still detected in sentinel animals, suggesting disease activity in the sylvatic cycle. The present study [...] Read more.
Yersinia pestis, the etiological agent of the plague, is considered a genetically homogeneous species. Brazil is currently in a period of epidemiological silence but plague antibodies are still detected in sentinel animals, suggesting disease activity in the sylvatic cycle. The present study deployed an in silico approach to analyze virulence factors among 407 Brazilian genomes of Y. pestis belonging to the Fiocruz Collection (1966–1997). The pangenome analysis associated several known virulence factors of Y. pestis in clades according to the presence or absence of genes. Four main strain clades (C, E, G, and H) exhibited the absence of various virulence genes. Notably, clade G displayed the highest number of absent genes, while clade E showed a significant absence of genes related to the T6SS secretion system and clade H predominantly demonstrated the absence of plasmid-related genes. These results suggest attenuation of virulence in these strains over time. The cgMLST analysis associated genomic and epidemiological data highlighting evolutionary patterns related to the isolation years and outbreaks of Y. pestis in Brazil. Thus, the results contribute to the understanding of the genetic diversity and virulence within Y. pestis and the potential for utilizing genomic data in epidemiological investigations. Full article
(This article belongs to the Special Issue An Ancient Terror, Yersinia pestis: What's New?)
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12 pages, 1621 KiB  
Article
Trends from the Last Decade with Nontuberculous Mycobacteria Lung Disease (NTM-LD): Clinicians’ Perspectives in Regional Center of Pulmonology in Bydgoszcz, Poland
by Grzegorz Przybylski, Jakub Bukowski, Weronika Kowalska, Marta Pilaczyńska-Cemel and Dorota Krawiecka
Pathogens 2023, 12(8), 988; https://doi.org/10.3390/pathogens12080988 - 28 Jul 2023
Cited by 3 | Viewed by 1279
Abstract
Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and [...] Read more.
Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and assess the frequency and clinical relevance of isolation of NTM in the Regional Center of Pulmonology in Bydgoszcz, hospital of Northern Poland. Design: Clinical, radiological, and microbiological data were collected from all patients from whom NTM was isolated between 2013 and 2022. Data were reviewed retrospectively. Diagnostic criteria for NTM-LD published by the American Thoracic Society (ATS) were used to determine clinical relevance. Material and methods: The study comprised 81,985 clinical specimens submitted for mycobacterial culture in the Department of Microbiology at the Regional Center of Pulmonology in Bydgoszcz between 2013 and 2022. Clinical specimens were processed according to the standard procedure in mycobacteria laboratories in Poland. NTM strains were identified using analysis of mycolic acids by chromatography as well as GenoType NTM-DR, GenoType Mycobacterium AS, and GenoType Mycobacterium CM. Results: There were 395 patients with NTM strains between 2013 and 2022. Out of them, 149 cases met the diagnostic criteria of NTM-LD and were classified as definite cases. M. kansasii (n = 77) was the most common species in the group (51.68%), followed by M. avium complex (n = 46). Patients with NTM-LD were 22–88 years old (median age was 60 years). There were 81 men and 68 women. The most common symptoms were cough, hemoptysis, and fever. Radiological X-ray images were dominated by infiltrative lesions in the upper and middle lobe of the right lung with cavities; the changes were in the upper lobe of the left lung and on both sides of the chest. They were smokers in 61%. The most common concomitant diseases were chronic obstructive pulmonary disease (COPD), diabetes mellitus, pulmonary carcinoma, and human immunodeficiency virus (HIV) infection, and other immunodeficiencies. The most common treatment was isoniazid, ethambutol, rifampicin, and ofloxacin for 18 months with a minimum of 12 months of culture negativity. Conclusions: NTM-LD infections are present with other pulmonary illnesses and extrapulmonary diseases and may be connected to primary immunologic deficiencies. These diseases concern patients of all ages and have various clinical manifestations. M. kansasii and MAC are the most prevalent NTM isolates among respiratory samples in Northern Poland. In addition, an increase in MAC and a decrease in M. kansasii both in cultivation and the cause of NTM-LD were reported. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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17 pages, 2077 KiB  
Article
Corynebacterium ulcerans Infections in Eurasian Beavers (Castor fiber)
by Reinhard Sting, Catharina Pölzelbauer, Tobias Eisenberg, Rebecca Bonke, Birgit Blazey, Martin Peters, Karin Riße, Andreas Sing, Anja Berger, Alexandra Dangel and Jörg Rau
Pathogens 2023, 12(8), 979; https://doi.org/10.3390/pathogens12080979 - 26 Jul 2023
Cited by 1 | Viewed by 1299
Abstract
The Eurasian beaver (Castor fiber) has been reintroduced successfully in Germany since the 1990s. Since wildlife is an important source of zoonotic infectious diseases, monitoring of invasive and reintroduced species is crucial with respect to the One Health approach. Three Eurasian beavers [...] Read more.
The Eurasian beaver (Castor fiber) has been reintroduced successfully in Germany since the 1990s. Since wildlife is an important source of zoonotic infectious diseases, monitoring of invasive and reintroduced species is crucial with respect to the One Health approach. Three Eurasian beavers were found dead in the German federal states of Bavaria, North Rhine–Westphalia and Baden–Wuerttemberg in 2015, 2021 and 2022, respectively. During post-mortem examinations, Corynebacterium (C.) ulcerans could be isolated from the abscesses of two beavers and from the lungs of one of the animals. Identification of the bacterial isolates at the species level was carried out by spectroscopic analysis using MALDI-TOF MS, FT-IR and biochemical profiles and were verified by molecular analysis based on 16-23S internal transcribed spacer (ITS) region sequencing. Molecular characterization of the C. ulcerans isolates using whole-genome sequencing (WGS) revealed a genome size of about 2.5 Mbp and a GC content of 53.4%. Multilocus sequence typing (MLST) analysis classified all three isolates as the sequence type ST-332. A minimum spanning tree (MST) based on cgMLST allelic profiles, including 1211 core genes of the sequenced C. ulcerans isolates, showed that the beaver-derived isolates clearly group on the branch of C. ulcerans with the closest relationship to each other, in close similarity to an isolate from a dog. Antibiotic susceptibility testing revealed resistance to clindamycin and, in one strain, to erythromycin according to EUCAST, while all isolates were susceptible to the other antimicrobials tested. Full article
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15 pages, 4500 KiB  
Article
Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge
by Stephen Findlay-Wilson, Lucy Flett, Francisco J. Salguero, Ines Ruedas-Torres, Susan Fotheringham, Linda Easterbrook, Victoria Graham and Stuart Dowall
Pathogens 2023, 12(8), 976; https://doi.org/10.3390/pathogens12080976 - 26 Jul 2023
Cited by 2 | Viewed by 1326
Abstract
Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through [...] Read more.
Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through exposure of infected pigs, ingestion of contaminated food, or through contact with an infected person. With no approved treatments or vaccines, NiV poses a threat to human public health and has epidemic potential. To aid with the assessment of emerging interventions being developed, an expansion of preclinical testing capability is required. Given variations in the model parameters observed in different sites during establishment, optimisation of challenge routes and doses is required. Upon evaluating the hamster model, an intranasal route of challenge was compared with intraperitoneal delivery, demonstrating a more rapid dissemination to wider tissues in the latter. A dose effect was observed between those causing respiratory illness and those resulting in neurological disease. The data demonstrate the successful establishment of the hamster model of NiV disease for subsequent use in the evaluation of vaccines and antivirals. Full article
(This article belongs to the Special Issue Emerging Viruses and Viral Zoonoses)
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13 pages, 286 KiB  
Review
The Importance of the One Health Concept in Combating Zoonoses
by Elina Horefti
Pathogens 2023, 12(8), 977; https://doi.org/10.3390/pathogens12080977 - 26 Jul 2023
Cited by 3 | Viewed by 2065
Abstract
One Health fundamentally acknowledges that human health is linked to animal health and the environment. One of the pillars One Health is built on is zoonoses. Through the years, zoonotic infections have caused numerous outbreaks and pandemics, as well as millions of fatalities, [...] Read more.
One Health fundamentally acknowledges that human health is linked to animal health and the environment. One of the pillars One Health is built on is zoonoses. Through the years, zoonotic infections have caused numerous outbreaks and pandemics, as well as millions of fatalities, with the COVID-19 pandemic being the latest one. Apart from the consequences to public health, zoonoses also affect society and the economy. Since its establishment, One Health has contributed significantly to the protection of humans, animals, and the environment, through preparedness, surveillance, and mitigation of such public dangers. Full article
(This article belongs to the Special Issue One Health: New Approaches, Research and Innovation to Zoonoses)
20 pages, 1592 KiB  
Article
Assessing Onchocerca volvulus Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment
by Shannon M. Hedtke, Young-Jun Choi, Anusha Kode, Gowtam C. Chalasani, Neha Sirwani, Stephen R. Jada, An Hotterbeekx, Michel Mandro, Joseph N. Siewe Fodjo, Glory Ngongeh Amambo, Raphael A. Abong, Samuel Wanji, Annette C. Kuesel, Robert Colebunders, Makedonka Mitreva and Warwick N. Grant
Pathogens 2023, 12(7), 971; https://doi.org/10.3390/pathogens12070971 - 24 Jul 2023
Cited by 3 | Viewed by 1466
Abstract
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi [...] Read more.
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4–5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample (n = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission. Full article
(This article belongs to the Section Parasitic Pathogens)
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22 pages, 13797 KiB  
Article
Art of the Kill: Designing and Testing Viral Inactivation Procedures for Highly Pathogenic Negative Sense RNA Viruses
by Judith Olejnik, Adam J. Hume, Stephen J. Ross, Whitney A. Scoon, Scott Seitz, Mitchell R. White, Ben Slutzky, Nadezhda E. Yun and Elke Mühlberger
Pathogens 2023, 12(7), 952; https://doi.org/10.3390/pathogens12070952 - 19 Jul 2023
Cited by 2 | Viewed by 2744
Abstract
The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the [...] Read more.
The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the inactivation procedures, which comes with an array of challenges for each method. This includes the use of cytotoxic reagents for chemical inactivation and defining the precise inactivation parameters for physical inactivation. Here, we provide a workflow for various inactivation methods using Ebola, Nipah, and Lassa viruses as our examples. We choose three distinct inactivation methods (TRIzol/TRIzol LS, aldehyde fixation using different fixatives, and heat) to highlight the challenges of each method and provide possible solutions. We show that, whereas published chemical inactivation methods are highly reliable, the parameters for heat inactivation must be clearly defined to ensure complete inactivation. In addition to the inactivation data, we also provide examples and templates for the documentation required for approval and use of inactivation SOPs, including an inactivation report, the procedure sections of developed SOPs, and an electronic inactivation certificate that accompanies inactivated samples. The provided information can be used as a roadmap for similar studies at high and maximum containment laboratories. Full article
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9 pages, 474 KiB  
Article
Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens
by Salvatore Martini, Mariantonietta Pisaturo, Antonio Russo, Maria Grazia Palamone, Maria Teresa Russo, Verdiana Zollo, Paolo Maggi and Nicola Coppola
Pathogens 2023, 12(7), 925; https://doi.org/10.3390/pathogens12070925 - 10 Jul 2023
Cited by 4 | Viewed by 955
Abstract
Background: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. [...] Read more.
Background: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. The aim of our study was to evaluate whether patients treated with PIs have both greater dyslipidemia and increased intima media thickness (IMT) and atheromatous plaques compared to patients treated without PIs. Materials and Methods: A total of 110 HIV-experienced patients screened with Doppler ultrasonography of the supra-aortic trunks in December 2019 were enrolled in a retrospective cross-sectional observational study. Patients were divided into two groups: 59 in the PI-based group, treated with PIs, and 51 in the PI-sparing group. In the two groups, we evaluated lipids, cardiovascular risk factors (smoking, BMI, age, hypertension), increased pathological IMT (a value > 1 mm), and possible atheromatous plaque. Results: Serum LDL (p 0.04) and percentage of patients with hypercholesterolemia (p 0.03) were higher in the PI-based than in the PI-sparing group. Doppler data showed a trend in increase of IMT > 1 in the PI-based group, which appeared statistically significant for the section of the left common carotid artery (p 0.03). However, in multivariate logistic regression models, none of the evaluated variables were significantly associated with IMT > 1. Conclusions: Our real-life data show that patients treated with PIs have a trend of developing both greater dyslipidemia and increased pathological IMT and atheromatous plaques These findings may be useful to optimize antiretrovirals for patients with cardiovascular risk factors. Full article
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20 pages, 2738 KiB  
Article
Helminths in Invasive Raccoons (Procyon lotor) from Southwest Germany
by Nico P. Reinhardt, Marion Wassermann, Jessica Härle, Thomas Romig, Lina Kurzrock, Janosch Arnold, Ernst Großmann, Ute Mackenstedt and Reinhard K. Straubinger
Pathogens 2023, 12(7), 919; https://doi.org/10.3390/pathogens12070919 - 08 Jul 2023
Cited by 4 | Viewed by 1542
Abstract
As hosts of numerous zoonotic pathogens, the role of raccoons needs to be considered in the One Health context. Raccoons progressively expand their range as invasive alien species in Europe. This study aimed to investigate the intestinal helminth fauna of raccoons in Baden-Wuerttemberg, [...] Read more.
As hosts of numerous zoonotic pathogens, the role of raccoons needs to be considered in the One Health context. Raccoons progressively expand their range as invasive alien species in Europe. This study aimed to investigate the intestinal helminth fauna of raccoons in Baden-Wuerttemberg, Germany, as no such screening had ever been conducted there. In total, we obtained 102 animals from hunters in 2019 and 2020. Intestinal helminths were retrieved using the SSCT (segmented sedimentation and counting technique) and identified morphologically and by PCR-based Sanger sequencing. Fecal samples were assessed using the ELISA PetChekTM IP assay (IDEXX, Germany) and flotation technique. The artificial digestion method was employed for analyzing muscle tissue. We detected species of four nematode genera (Baylisascaris procyonis, Toxocara canis, Capillaria spp., and Trichuris spp.), three cestode genera (Atriotaenia cf. incisa/procyonis, Taenia martis, and Mesocestoides spp.), and three trematode genera (Isthmiophora hortensis/melis, Plagiorchis muris, and Brachylaima spp.). Echinococcus spp. and Trichinella spp. were not found. The invasive behavior and synanthropic habits of raccoons may increase the infection risk with these helminths in wildlife, domestic and zoo animals, and humans by serving as a connecting link. Therefore, it is crucial to initiate additional studies assessing these risks. Full article
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14 pages, 1942 KiB  
Article
Role of D(−)-Lactic Acid in Prevention of Chlamydia trachomatis Infection in an In Vitro Model of HeLa Cells
by Chiara Zalambani, Nicola Rizzardi, Giacomo Marziali, Claudio Foschi, Sara Morselli, Marielle Ezekielle Djusse, Marina Naldi, Romana Fato, Natalia Calonghi and Antonella Marangoni
Pathogens 2023, 12(7), 883; https://doi.org/10.3390/pathogens12070883 - 28 Jun 2023
Cited by 3 | Viewed by 1251
Abstract
A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic [...] Read more.
A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic acid isomer are known to exert stronger protection. However, the molecular mechanisms underlying this antimicrobial action are not well understood. The aim of this study was to investigate the role of D(−)-lactic acid isomer in the prevention of C. trachomatis infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of Lactobacillus crispatus that releases both D(−) and L(+) isomers and a strain of Lactobacillus reuteri that produces only the L(+) isomer. Initially, we demonstrated that L. crispatus was significantly more effective than L. reuteri in reducing C. trachomatis infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of Lactobacillus crispatus or L. reuteri, resulting in different transcription of genes such as CCND1, CDKN1A, ITAG5 and HER-1. Similarly, distinct transcription patterns were found in HeLa cells treated with 10 mM D(−)- or L(+)-lactic acid isomers. Our findings suggest that D(−) lactic acid significantly affects two non-exclusive mechanisms involved in C. trachomatis infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin. Full article
(This article belongs to the Special Issue Chlamydia trachomatis: Innate Immunity, Vaccines and Behaviour)
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17 pages, 1705 KiB  
Article
Quantitative Risk Assessment of Oocyst Versus Bradyzoite Foodborne Transmission of Toxoplasma gondii in Brazil
by Sophie Zhu, Elizabeth VanWormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto DaMatta, Pedro Souto Rodrigues and Karen Shapiro
Pathogens 2023, 12(7), 870; https://doi.org/10.3390/pathogens12070870 - 25 Jun 2023
Cited by 3 | Viewed by 1256
Abstract
Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental [...] Read more.
Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in Brazil. Oocyst contamination in fruits and greens contributed significantly more to overall estimated T. gondii infections than bradyzoite-contaminated foods (beef, pork, poultry). In sensitivity analysis, treatment, i.e., cooking temperature for meat and washing efficiency for produce, most strongly affected the estimated toxoplasmosis incidence rate. Due to the lack of regional food contamination prevalence data and the high level of uncertainty in many model parameters, this analysis provides an initial estimate of the relative importance of food products. Important knowledge gaps for oocyst-borne infections were identified and can drive future studies to improve risk assessments and effective policy actions to reduce human toxoplasmosis in Brazil. Full article
(This article belongs to the Special Issue Toxoplasma gondii and Food Safety)
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21 pages, 5354 KiB  
Article
Newly Designed Poxviral Promoters to Improve Immunogenicity and Efficacy of MVA-NP Candidate Vaccines against Lethal Influenza Virus Infection in Mice
by Martin C. Langenmayer, Anna-Theresa Luelf-Averhoff, Lisa Marr, Sylvia Jany, Astrid Freudenstein, Silvia Adam-Neumair, Alina Tscherne, Robert Fux, Juan J. Rojas, Andreas Blutke, Gerd Sutter and Asisa Volz
Pathogens 2023, 12(7), 867; https://doi.org/10.3390/pathogens12070867 - 23 Jun 2023
Cited by 2 | Viewed by 1250
Abstract
Influenza, a respiratory disease mainly caused by influenza A and B, viruses of the Orthomyxoviridae, is still a burden on our society’s health and economic system. Influenza A viruses (IAV) circulate in mammalian and avian populations, causing seasonal outbreaks with high numbers [...] Read more.
Influenza, a respiratory disease mainly caused by influenza A and B, viruses of the Orthomyxoviridae, is still a burden on our society’s health and economic system. Influenza A viruses (IAV) circulate in mammalian and avian populations, causing seasonal outbreaks with high numbers of cases. Due to the high variability in seasonal IAV triggered by antigenic drift, annual vaccination is necessary, highlighting the need for a more broadly protective vaccine against IAV. The safety tested Modified Vaccinia virus Ankara (MVA) is licensed as a third-generation vaccine against smallpox and serves as a potent vector system for the development of new candidate vaccines against different pathogens. Here, we generated and characterized recombinant MVA candidate vaccines that deliver the highly conserved internal nucleoprotein (NP) of IAV under the transcriptional control of five newly designed chimeric poxviral promoters to further increase the immunogenic properties of the recombinant viruses (MVA-NP). Infections of avian cell cultures with the recombinant MVA-NPs demonstrated efficient synthesis of the IAV-NP which was expressed under the control of the five new promoters. Prime-boost or single shot immunizations in C57BL/6 mice readily induced circulating serum antibodies’ binding to recombinant IAV-NP and the robust activation of IAV-NP-specific CD8+ T cell responses. Moreover, the MVA-NP candidate vaccines protected C57BL/6 mice against lethal respiratory infection with mouse-adapted IAV (A/Puerto Rico/8/1934/H1N1). Thus, further studies are warranted to evaluate the immunogenicity and efficacy of these recombinant MVA-NP vaccines in other IAV challenge models in more detail. Full article
(This article belongs to the Special Issue Animal Models for Human Viruses)
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16 pages, 2154 KiB  
Review
The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic
by Linda Petrone, Alessandro Sette, Rory D. de Vries and Delia Goletti
Pathogens 2023, 12(7), 862; https://doi.org/10.3390/pathogens12070862 - 22 Jun 2023
Cited by 8 | Viewed by 1526
Abstract
Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell [...] Read more.
Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell responses after vaccination largely mirror those of natural infection in magnitude and functional capacity, but not in breadth, as T-cells induced by vaccination exclusively target the surface spike glycoprotein. T-cell responses offer a long-lived line of defense and, unlike humoral responses, largely retain reactivity against the SARS-CoV-2 variants. Given the increasingly recognized role of T-cell responses in protection against severe COVID-19, the circulation of SARS-CoV-2 variants, and the potential implementation of novel vaccines, it becomes imperative to continuously monitor T-cell responses. In addition to “classical” T-cell assays requiring the isolation of peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release assays have a potential role in routine T-cell response monitoring. These assays could be particularly useful for immunocompromised people and other clinically vulnerable populations, where interactions between cellular and humoral immunity are complex. As we continue to live alongside COVID-19, the importance of considering immunity as a whole, incorporating both humoral and cellular responses, is crucial. Full article
(This article belongs to the Collection SARS-CoV-2 Infection and COVID-19 Disease)
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