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Volume 10
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Pathogens, Volume 10, Issue 7 (July 2021) – 133 articles

Cover Story (view full-size image): Francisella tularensis (Ft) is a Tier 1 Select Agent of concern for biodefense for which there is no licensed vaccine. Herein, the Ft transporters, FptA and FptF, are evaluated as targets for attenuating mutations in Ft LVS. ΔfptA and ΔfptF mutant strains are attenuated and confer protection against lethal challenge in the mouse model. Furthermore, the data support roles for both transporters in modulating the host immune response to promote Ft’s full virulence. The results support a fundamental requirement for FptA and FptF in the pathogenesis of Ft and their potential as targets in Ft vaccine development. View this paper.
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22 pages, 3860 KiB  
Article
Cerebral Organoids Derived from a Parkinson’s Patient Exhibit Unique Pathogenesis from Chikungunya Virus Infection When Compared to a Non-Parkinson’s Patient
by Emily M. Schultz, TyAnthony J. Jones, Sibei Xu, Dana D. Dean, Bernd Zechmann and Kelli L. Barr
Pathogens 2021, 10(7), 913; https://doi.org/10.3390/pathogens10070913 - 20 Jul 2021
Cited by 8 | Viewed by 3123
Abstract
(1) Background: Arboviruses of medical and veterinary significance have been identified on all seven continents, with every human and animal population at risk for exposure. Like arboviruses, chronic neurodegenerative diseases, like Alzheimer’s and Parkinson’s disease, are found wherever there are humans. Significant differences [...] Read more.
(1) Background: Arboviruses of medical and veterinary significance have been identified on all seven continents, with every human and animal population at risk for exposure. Like arboviruses, chronic neurodegenerative diseases, like Alzheimer’s and Parkinson’s disease, are found wherever there are humans. Significant differences in baseline gene and protein expression have been determined between human-induced pluripotent stem cell lines derived from non-Parkinson’s disease individuals and from individuals with Parkinson’s disease. It was hypothesized that these inherent differences could impact cerebral organoid responses to viral infection. (2) Methods: In this study, cerebral organoids from a non-Parkinson’s and Parkinson’s patient were infected with Chikungunya virus and observed for two weeks. (3) Results: Parkinson’s organoids lost mass and exhibited a differential antiviral response different from non-Parkinson’s organoids. Neurotransmission data from both infected non-Parkinson’s and Parkinson’s organoids had dysregulation of IL-1, IL-10, and IL-6. These cytokines are associated with mood and could be contributing to persistent depression seen in patients following CHIKV infection. Both organoid types had increased expression of CXCL10, which is linked to demyelination. (4) Conclusions: The differential antiviral response of Parkinson’s organoids compared with non-Parkinson’s organoids highlights the need for more research in neurotropic infections in a neurologically compromised host. Full article
(This article belongs to the Collection Feature Papers in Viral Pathogens)
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30 pages, 2788 KiB  
Article
Evidence of Immune Modulators in the Secretome of the Equine Tapeworm Anoplocephala perfoliata
by Boontarikaan Wititkornkul, Benjamin J. Hulme, John J. Tomes, Nathan R. Allen, Chelsea N. Davis, Sarah D. Davey, Alan R. Cookson, Helen C. Phillips, Matthew J. Hegarty, Martin T. Swain, Peter M. Brophy, Ruth E. Wonfor and Russell M. Morphew
Pathogens 2021, 10(7), 912; https://doi.org/10.3390/pathogens10070912 - 20 Jul 2021
Cited by 8 | Viewed by 3630
Abstract
Anoplocephala perfoliata is a neglected gastro-intestinal tapeworm, commonly infecting horses worldwide. Molecular investigation of A. perfoliata is hampered by a lack of tools to better understand the host–parasite interface. This interface is likely influenced by parasite derived immune modulators released in the secretome [...] Read more.
Anoplocephala perfoliata is a neglected gastro-intestinal tapeworm, commonly infecting horses worldwide. Molecular investigation of A. perfoliata is hampered by a lack of tools to better understand the host–parasite interface. This interface is likely influenced by parasite derived immune modulators released in the secretome as free proteins or components of extracellular vesicles (EVs). Therefore, adult RNA was sequenced and de novo assembled to generate the first A. perfoliata transcriptome. In addition, excretory secretory products (ESP) from adult A. perfoliata were collected and EVs isolated using size exclusion chromatography, prior to proteomic analysis of the EVs, the EV surface and EV depleted ESP. Transcriptome analysis revealed 454 sequences homologous to known helminth immune modulators including two novel Sigma class GSTs, five α-HSP90s, and three α-enolases with isoforms of all three observed within the proteomic analysis of the secretome. Furthermore, secretome proteomics identified common helminth proteins across each sample with known EV markers, such as annexins and tetraspanins, observed in EV fractions. Importantly, 49 of the 454 putative immune modulators were identified across the secretome proteomics contained within and on the surface of EVs in addition to those identified in free ESP. This work provides the molecular tools for A. perfoliata to reveal key players in the host–parasite interaction within the horse host. Full article
(This article belongs to the Special Issue Proteomics of Host-Helminth Interactions)
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11 pages, 467 KiB  
Study Protocol
Nationwide Seroprevalence of SARS-CoV-2 IgG Antibodies among Four Groups of Primary Health-Care Workers and Their Household Contacts 6 Months after the Initiation of the COVID-19 Vaccination Campaign in France: SeroPRIM Study Protocol
by Marie Pouquet, Dorine Decarreaux, Pol Prévot-Monsacré, Corentin Hervé, Andréas Werner, Brigitte Grosgogeat, Hélène Blanché, Pascaline Rabiega, Julien Laupie, Fabienne Kochert, Nathalie Abraham, Jean-Marc Sebaoun, Xavier de Lamballerie, Remi Charrel, Cecile Souty, Ibrahima Camara, Jeanne Pergeline, Harold Noël, Caroline Guerrisi, Sylvie van der Werf, Fabrice Carrat, Thomas Hanslik, Thierry Blanchon and Alessandra Falchiadd Show full author list remove Hide full author list
Pathogens 2021, 10(7), 911; https://doi.org/10.3390/pathogens10070911 - 20 Jul 2021
Cited by 6 | Viewed by 2695
Abstract
Background: The protocol study will focus on the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection as well as the history, symptoms, and risk factors for SARS-CoV-2 in four primary health-care workers (PHCWs) and their household contacts in metropolitan [...] Read more.
Background: The protocol study will focus on the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection as well as the history, symptoms, and risk factors for SARS-CoV-2 in four primary health-care workers (PHCWs) and their household contacts in metropolitan France. Methods: Here, we propose a protocol for a nationwide survey to determine the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection in four PHCW populations (general practitioners, pediatricians, pharmacists and assistants, and dentists and assistants) and their household contacts. Participants will be included from June to July 2021 (Phase 1) among PHCW populations located throughout metropolitan France. They will be asked to provide a range of demographic and behavioral information since the first SARS-CoV-2 wave and a self-sampled dried blood spot. Phase 1 will involve also a questionnaire and serological study of PHCWs’ household contacts. Seroprevalence will be estimated using two ELISAs designed to detect specific IgG antibodies to SARS-CoV-2 in humoral fluid, and these results will be confirmed using a virus neutralization test. This study will be repeated from November to December 2021 (Phase 2) to evaluate the evolution of immune status achieved by vaccination and/or natural protection of PHCWs and to describe the history of exposure to SARS-CoV-2. Full article
(This article belongs to the Collection Emerging and Re-emerging Pathogens)
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20 pages, 1610 KiB  
Article
Molecular Characterization of the env Gene of Bovine Leukemia Virus in Cattle from Pakistan with NGS-Based Evidence of Virus Heterogeneity
by Marzena Rola-Łuszczak, Ali Sakhawat, Aneta Pluta, Anna Ryło, Arkadiusz Bomba, Nazia Bibi and Jacek Kuźmak
Pathogens 2021, 10(7), 910; https://doi.org/10.3390/pathogens10070910 - 19 Jul 2021
Cited by 6 | Viewed by 2928
Abstract
Characterization of the global genetic diversity of the bovine leukemia virus (BLV) is an ongoing international research effort. Up to now BLV sequences have been classified into eleven distinct genotypes. Although BLV genotyping and molecular analysis of field isolates were reported in many [...] Read more.
Characterization of the global genetic diversity of the bovine leukemia virus (BLV) is an ongoing international research effort. Up to now BLV sequences have been classified into eleven distinct genotypes. Although BLV genotyping and molecular analysis of field isolates were reported in many countries, there is no report describing BLV genotypes present in cattle from Pakistan. In this study we examined 27 env gene sequences from BLV-infected cattle coming from four farms located in Khyber Pakhtunkwa, Gilgit Baltisan and Punjab provinces. Phylogenetic analyses revealed the classification of Pakistani sequences into genotypes G1 and G6. The alignment with the FLK-BLV sequence revealed the presence of 45 mutations, namely, seven in genotype G1 and 33 in genotype G6. Five mutations were found in both, G1 and G6 genotypes. Twelve amino acid substitutions were found in the analyzed sequences, of which only one P264S was specific for sequences from Pakistan. Furthermore, a certain degree of nucleotide heterogeneity was identified by NGS. These results highlight the need for further study on the importance of genetic variability of BLV, especially in the context of its pathogenicity and potential effect on serological detection. Full article
(This article belongs to the Collection Bovine Leukemia Virus Infection)
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15 pages, 1222 KiB  
Article
Natural Transformation as a Mechanism of Horizontal Gene Transfer in Aliarcobacter butzleri
by Marina Bonifácio, Cristiana Mateus, Ana R. Alves, Emanuel Maldonado, Ana P. Duarte, Fernanda Domingues, Mónica Oleastro and Susana Ferreira
Pathogens 2021, 10(7), 909; https://doi.org/10.3390/pathogens10070909 - 19 Jul 2021
Cited by 6 | Viewed by 2485
Abstract
Aliarcobacter butzleri is an emergent enteropathogen, showing high genetic diversity, which likely contributes to its adaptive capacity to different environments. Whether natural transformation can be a mechanism that generates genetic diversity in A. butzleri is still unknown. In the present study, we aimed [...] Read more.
Aliarcobacter butzleri is an emergent enteropathogen, showing high genetic diversity, which likely contributes to its adaptive capacity to different environments. Whether natural transformation can be a mechanism that generates genetic diversity in A. butzleri is still unknown. In the present study, we aimed to establish if A. butzleri is naturally competent for transformation and to investigate the factors influencing this process. Two different transformation procedures were tested using exogenous and isogenic DNA containing antibiotic resistance markers, and different external conditions influencing the process were evaluated. The highest number of transformable A. butzleri strains were obtained with the agar transformation method when compared to the biphasic system (65% versus 47%). A. butzleri was able to uptake isogenic chromosomal DNA at different growth phases, and the competence state was maintained from the exponential to the stationary phases. Overall, the optimal conditions for transformation with the biphasic system were the use of 1 μg of isogenic DNA and incubation at 30 °C under a microaerobic atmosphere, resulting in a transformation frequency ~8 × 10−6 transformants/CFU. We also observed that A. butzleri favored the transformation with the genetic material of its own strain/species, with the DNA incorporation process occurring promptly after the addition of genomic material. In addition, we observed that A. butzleri strains could exchange genetic material in co-culture assays. The presence of homologs of well-known genes involved in the competence in the A. butzleri genome corroborates the natural competence of this species. In conclusion, our results show that A. butzleri is a naturally transformable species, suggesting that horizontal gene transfer mediated by natural transformation is one of the processes contributing to its genetic diversity. In addition, natural transformation can be used as a tool for genetic studies of this species. Full article
(This article belongs to the Collection New Insights into Bacterial Pathogenesis)
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14 pages, 494 KiB  
Review
Licensing Natural Killers for Antiviral Immunity
by John M. Cronk, Eleni Fafoutis and Michael G. Brown
Pathogens 2021, 10(7), 908; https://doi.org/10.3390/pathogens10070908 - 19 Jul 2021
Cited by 5 | Viewed by 3756
Abstract
Immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors (IRs) enable discrimination between self- and non-self molecules on the surface of host target cells. In this regard, they have a vital role in self-tolerance through binding and activating intracellular tyrosine phosphatases which can inhibit cellular activation. [...] Read more.
Immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors (IRs) enable discrimination between self- and non-self molecules on the surface of host target cells. In this regard, they have a vital role in self-tolerance through binding and activating intracellular tyrosine phosphatases which can inhibit cellular activation. Yet, self-MHC class I (MHC I)-specific IRs are versatile in that they can also positively impact lymphocyte functionality, as exemplified by their role in natural killer (NK) cell education, often referred to as ’licensing‘. Recent discoveries using defined mouse models of cytomegalovirus (CMV) infection have revealed that select self-MHC I IRs can increase NK cell antiviral defenses as well, whereas other licensing IRs cannot, or instead impede virus-specific NK responses for reasons that remain poorly understood. This review highlights a role for self-MHC I ‘licensing’ IRs in antiviral immunity, especially in the context of CMV infection, their impact on virus-specific NK cells during acute infection, and their potential to affect viral pathogenesis and disease. Full article
(This article belongs to the Special Issue Murine Models of Cytomegalovirus Infection)
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10 pages, 263 KiB  
Article
Natural Infection of Dairy Cows with Bovine Leukemia Virus Affects Immunoglobulin Levels in Saliva and Serum but Not Milk
by Monika Dziuba, Vickie J. Ruggiero, Catherine Wilson, Paul C. Bartlett and Paul M. Coussens
Pathogens 2021, 10(7), 907; https://doi.org/10.3390/pathogens10070907 - 18 Jul 2021
Cited by 1 | Viewed by 2205
Abstract
Bovine leukemia virus (BLV) is a retroviral infection that disrupts the immune function of infected animals. It is widespread among U.S. dairy cattle. In this pilot study, the average total IgA and IgM concentrations in milk, saliva, and serum samples from BLV ELISA-positive [...] Read more.
Bovine leukemia virus (BLV) is a retroviral infection that disrupts the immune function of infected animals. It is widespread among U.S. dairy cattle. In this pilot study, the average total IgA and IgM concentrations in milk, saliva, and serum samples from BLV ELISA-positive (ELISA+) dairy cows were compared against samples from BLV ELISA-negative (ELISA−) cows using the Kruskal–Wallis test (with ties). The results from ELISA+ cows were also stratified by lymphocyte count (LC) and proviral load (PVL). In milk and saliva from ELISA+ cows, the average total IgA and IgM concentrations were decreased compared to ELISA− cows, although this was only statistically significant for saliva IgM in cows with low PVL (p = 0.0424). Numerically, the average total IgA concentrations were 33.6% lower in milk and 23.7% lower in saliva, and the average total IgM concentrations were 42.4% lower in milk and 15.5% lower in saliva. No significant differences were observed in the total serum IgA concentrations, regardless of PVL and LC. The total serum IgM from ELISA+ cows was significantly decreased (p = 0.0223), with the largest decreases occurring in the highest PVL and LC subgroups. This pilot study is a first step in investigating the impact of BLV on mucosal immunity and will require further exploration in each of the various stages of disease progression. Full article
(This article belongs to the Collection Bovine Leukemia Virus Infection)
11 pages, 273 KiB  
Review
Exploring the Ability of Meningococcal Vaccines to Elicit Mucosal Immunity: Insights from Humans and Mice
by Elissa G. Currie and Scott D. Gray-Owen
Pathogens 2021, 10(7), 906; https://doi.org/10.3390/pathogens10070906 - 18 Jul 2021
Cited by 2 | Viewed by 2683
Abstract
Neisseria meningitidis causes a devastating invasive disease but is also a normal colonizer of the human nasopharynx. Due to the rapid progression of disease, the best tool to protect individuals against meningococcal infections is immunization. Clinical experience with polysaccharide conjugate vaccines has revealed [...] Read more.
Neisseria meningitidis causes a devastating invasive disease but is also a normal colonizer of the human nasopharynx. Due to the rapid progression of disease, the best tool to protect individuals against meningococcal infections is immunization. Clinical experience with polysaccharide conjugate vaccines has revealed that an ideal meningococcal vaccine must prevent both invasive disease and nasal colonization, which confers herd immunity. However, not all meningococcal vaccines are equal in their ability to prevent nasal colonization, for unknown reasons. Herein, we describe recent efforts to utilize humanized mouse models to understand the impact of different meningococcal vaccines on nasal colonization. These mice are susceptible to nasal colonization, and they become immune following live nasal infection or immunization with matched capsule-conjugate or protein-based vaccines, replicating findings from human work. We bring together insights regarding meningococcal colonization and immunity from clinical work with findings using humanized mouse models, providing new perspective into the different determinants of mucosal versus systemic immunity. Then, we use this as a framework to help focus future studies toward understanding key mechanistic aspects left unresolved, including the bacterial factors required for colonization and immune evasion, determinants of nasal mucosal protection, and characteristics of an ideal meningococcal vaccine. Full article
(This article belongs to the Special Issue Meningococcal Disease in the Era of Multivalent Vaccines: Where Are We Now and Can We Do Better?)
19 pages, 2778 KiB  
Review
The Role of Macrophages in the Host’s Defense against Sporothrix schenckii
by Estela Ruiz-Baca, Armando Pérez-Torres, Yolanda Romo-Lozano, Daniel Cervantes-García, Carlos A. Alba-Fierro, Javier Ventura-Juárez and Conchita Torriello
Pathogens 2021, 10(7), 905; https://doi.org/10.3390/pathogens10070905 - 18 Jul 2021
Cited by 15 | Viewed by 4176
Abstract
The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological [...] Read more.
The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host–pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host–pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus. Full article
(This article belongs to the Special Issue Identification and Infection of Sporothrix schenckii)
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15 pages, 2841 KiB  
Article
Characterization of Oral Microbiota in Cats: Novel Insights on the Potential Role of Fungi in Feline Chronic Gingivostomatitis
by Janina A. Krumbeck, Alexander M. Reiter, James C. Pohl, Shuiquan Tang, Young J. Kim, Annika Linde, Aishani Prem and Tonatiuh Melgarejo
Pathogens 2021, 10(7), 904; https://doi.org/10.3390/pathogens10070904 - 17 Jul 2021
Cited by 13 | Viewed by 5076
Abstract
Previous studies have suggested the involvement of viral and bacterial components in the initiation and progression of feline chronic gingivostomatitis (FCGS), but the role of fungi remains entirely unknown. This pilot study aimed to investigate the bacteriome and mycobiome in feline oral health [...] Read more.
Previous studies have suggested the involvement of viral and bacterial components in the initiation and progression of feline chronic gingivostomatitis (FCGS), but the role of fungi remains entirely unknown. This pilot study aimed to investigate the bacteriome and mycobiome in feline oral health and disease. Physical exams, including oral health assessment, of privately owned, clinically healthy (CH) cats (n = 14) and cats affected by FCGS (n = 14) were performed. Using a sterile swab, oral tissue surfaces of CH and FCGS cats were sampled and submitted for 16S rRNA and ITS-2 next-generation DNA sequencing. A high number of fungal species (n = 186) was detected, with Malassezia restricta, Malassezia arunalokei, Cladosporium penidielloides/salinae, and Aspergillaceae sp. being significantly enriched in FCGS samples, and Saccharomyces cerevisiae in CH samples. The bacteriome was significantly distinct between groups, and significant inter-kingdom interactions were documented. Bergeyella zoohelcum was identified as a potential biomarker of a healthy feline oral microbiome. These data suggest that fungi might play a role in the etiology and pathogenesis of FCGS, and that oral health should not simply be regarded as the absence of microbial infections. Instead, it may be viewed as the biological interactions between bacterial and fungal populations that coexist to preserve a complex equilibrium in the microenvironment of the mouth. Additional investigations are needed to improve our understanding of the feline oral ecosystem and the potential interactions between viruses, bacteria, and fungi in FCGS. Full article
(This article belongs to the Section Fungal Pathogens)
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11 pages, 1992 KiB  
Article
Biological Control of Take-All and Growth Promotion in Wheat by Pseudomonas chlororaphis YB-10
by Wen Xu, Lingling Xu, Xiaoxu Deng, Paul H. Goodwin, Mingcong Xia, Jie Zhang, Qi Wang, Runhong Sun, Yamei Pan, Chao Wu and Lirong Yang
Pathogens 2021, 10(7), 903; https://doi.org/10.3390/pathogens10070903 - 17 Jul 2021
Cited by 14 | Viewed by 2948
Abstract
Wheat is a worldwide staple food crop, and take-all caused by Gaeumannomyces graminis var. tritici can lead to a tremendous decrease in wheat yield and quality. In this study, strain YB-10 was isolated from wheat rhizospheric soil and identified as Pseudomonas chlororaphis by [...] Read more.
Wheat is a worldwide staple food crop, and take-all caused by Gaeumannomyces graminis var. tritici can lead to a tremendous decrease in wheat yield and quality. In this study, strain YB-10 was isolated from wheat rhizospheric soil and identified as Pseudomonas chlororaphis by morphology and 16S rRNA gene sequencing. Pseudomonas chlororaphis YB-10 had extracellular protease and cellulase activities and strongly inhibited the mycelium growth of Gaeumannomyces graminis var. tritici in dual cultures. Up to 87% efficacy of Pseudomonas chlororaphis YB-10 in controlling the take-all of seedlings was observed in pot experiments when wheat seed was coated with the bacterium. Pseudomonas chlororaphis YB-10 was also positive for indole acetic acid (IAA) and siderophore production, and coating wheat seed with the bacterium significantly promoted the growth of seedlings at 107 and 108 CFU/mL. Furthermore, treatment with Pseudomonas chlororaphis YB-10 increased activities of the wheat defense-related enzymes POD, SOD, CAT, PAL and PPO in seedlings, indicating induced resistance against pathogens. Overall, Pseudomonas chlororaphis YB-10 is a promising new seed-coating agent to both promote wheat growth and suppress take-all. Full article
(This article belongs to the Special Issue Potential of Plant Growth-Promoting and Biocontrol Microorganisms in Controlling Plant Diseases)
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15 pages, 1884 KiB  
Review
Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches
by Carla E. Gallardo-Flores and Che C. Colpitts
Pathogens 2021, 10(7), 902; https://doi.org/10.3390/pathogens10070902 - 17 Jul 2021
Cited by 4 | Viewed by 4584
Abstract
Cyclophilins are cellular peptidyl-prolyl isomerases that play an important role in viral infections, with demonstrated roles in the replication of hepatitis C virus (HCV) and other viruses in the Flaviviridae family, such as dengue virus (DENV) and yellow fever virus (YFV). Here, we [...] Read more.
Cyclophilins are cellular peptidyl-prolyl isomerases that play an important role in viral infections, with demonstrated roles in the replication of hepatitis C virus (HCV) and other viruses in the Flaviviridae family, such as dengue virus (DENV) and yellow fever virus (YFV). Here, we discuss the roles of cyclophilins in HCV infection and provide a comprehensive overview of the mechanisms underlying the requirement for cyclophilins during HCV replication. Notably, cyclophilin inhibitor therapy has been demonstrated to be effective in reducing HCV replication in chronically infected patients. While the roles of cyclophilins are relatively well-understood for HCV infection, cyclophilins are more recently emerging as host factors for flavivirus infection as well, providing potential new therapeutic avenues for these viral infections which currently lack antiviral therapies. However, further studies are required to elucidate the roles of cyclophilins in flavivirus replication. Here, we review the current knowledge of the role of cyclophilins in HCV infection to provide a conceptual framework to understand how cyclophilins may contribute to other viral infections, such as DENV and YFV. Improved understanding of the roles of cyclophilins in viral infection may open perspectives for the development of cyclophilin inhibitors as effective antiviral therapeutics for HCV and related viruses. Full article
(This article belongs to the Special Issue Hepatitis C Virus: Remaining Challenges)
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16 pages, 3948 KiB  
Article
Selection for Plastic, Pathogen-Inducible Recombination in a Red Queen Model with Diploid Antagonists
by Sviatoslav Rybnikov, Zeev Frenkel, Abraham B. Korol and Tzion Fahima
Pathogens 2021, 10(7), 898; https://doi.org/10.3390/pathogens10070898 - 16 Jul 2021
Cited by 3 | Viewed by 2005
Abstract
Antagonistic interactions and co-evolution between a host and its parasite are known to cause oscillations in the population genetic structure of both species (Red Queen dynamics). Potentially, such oscillations may select for increased sex and recombination in the host, although theoretical models suggest [...] Read more.
Antagonistic interactions and co-evolution between a host and its parasite are known to cause oscillations in the population genetic structure of both species (Red Queen dynamics). Potentially, such oscillations may select for increased sex and recombination in the host, although theoretical models suggest that this happens under rather restricted values of selection intensity, epistasis, and other parameters. Here, we explore a model in which the diploid parasite succeeds to infect the diploid host only if their phenotypes at the interaction-mediating loci match. Whenever regular oscillations emerge in this system, we test whether plastic, pathogen-inducible recombination in the host can be favored over the optimal constant recombination. Two forms of the host recombination dependence on the parasite pressure were considered: either proportionally to the risk of infection (prevention strategy) or upon the fact of infection (remediation strategy). We show that both forms of plastic recombination can be favored, although relatively infrequently (up to 11% of all regimes with regular oscillations, and up to 20% of regimes with obligate parasitism). This happens under either strong overall selection and high recombination rate in the host, or weak overall selection and low recombination rate in the host. In the latter case, the system’s dynamics are considerably more complex. The prevention strategy is favored more often than the remediation one. It is noteworthy that plastic recombination can be favored even when any constant recombination is rejected, making plasticity an evolutionary mechanism for the rescue of host recombination. Full article
(This article belongs to the Special Issue Genomics, Molecular, Genetics, and Diversity of Plant Disease Resistance)
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9 pages, 980 KiB  
Article
Detection of Tick-Borne Pathogens of the Genera Rickettsia, Anaplasma and Francisella in Ixodes ricinus Ticks in Pomerania (Poland)
by Lucyna Kirczuk, Mariusz Piotrowski and Anna Rymaszewska
Pathogens 2021, 10(7), 901; https://doi.org/10.3390/pathogens10070901 - 15 Jul 2021
Cited by 5 | Viewed by 2072
Abstract
Tick-borne pathogens are an important medical and veterinary issue worldwide. Environmental monitoring in relation to not only climate change but also globalization is currently essential. The present study aimed to detect tick-borne pathogens of the genera Anaplasma, Rickettsia and Francisella in Ixodes [...] Read more.
Tick-borne pathogens are an important medical and veterinary issue worldwide. Environmental monitoring in relation to not only climate change but also globalization is currently essential. The present study aimed to detect tick-borne pathogens of the genera Anaplasma, Rickettsia and Francisella in Ixodes ricinus ticks collected from the natural environment, i.e., recreational areas and pastures used for livestock grazing. A total of 1619 specimens of I. ricinus were collected, including ticks of all life stages (adults, nymphs and larvae). The study was performed using the PCR technique. Diagnostic gene fragments msp2 for Anaplasma, gltA for Rickettsia and tul4 for Francisella were amplified. No Francisella spp. DNA was detected in I. ricinus. DNA of A. phagocytophilum was detected in 0.54% of ticks and Rickettsia spp. in 3.69%. Nucleotide sequence analysis revealed that only one species of Rickettsia, R. helvetica, was present in the studied tick population. The present results are a part of a large-scale analysis aimed at monitoring the level of tick infestation in Northwest Poland. Full article
(This article belongs to the Special Issue Ticks and Tick-Borne Diseases―Pathogens, Parasites and People)
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13 pages, 5363 KiB  
Article
Microbiological Quality of Nuts, Dried and Candied Fruits, Including the Prevalence of Cronobacter spp.
by Anna Berthold-Pluta, Monika Garbowska, Ilona Stefańska, Lidia Stasiak-Różańska, Tamara Aleksandrzak-Piekarczyk and Antoni Pluta
Pathogens 2021, 10(7), 900; https://doi.org/10.3390/pathogens10070900 - 15 Jul 2021
Cited by 7 | Viewed by 5486
Abstract
Cronobacter genus bacteria are food-borne pathogens. Foods contaminated with Cronobacter spp. may pose a risk to infants or immunocompromised adults. The aim of this study was to determine the microbiological quality of nuts, seeds and dried fruits with special emphasis on the occurrence [...] Read more.
Cronobacter genus bacteria are food-borne pathogens. Foods contaminated with Cronobacter spp. may pose a risk to infants or immunocompromised adults. The aim of this study was to determine the microbiological quality of nuts, seeds and dried fruits with special emphasis on the occurrence of Cronobacter spp. Analyses were carried out on 64 samples of commercial nuts (20 samples), dried fruits (24), candied fruits (8), seeds (4), and mixes of seeds, dried fruits and nuts (8). The samples were tested for the total plate count of bacteria (TPC), counts of yeasts and molds, and the occurrence of Cronobacter spp. Cronobacter isolates were identified and differentiated by PCR-RFLP (Polymerase Chain Reaction - Restriction Fragments Length Polymorphism) and RAPD-PCR (Random Amplified Polymorphic DNA by PCR) analysis. TPC, and yeasts and molds were not detected in 0.1 g of 23.4%, 89.1%, and 32.8% of the analyzed samples. In the remaining samples, TPC were in the range of 1.2–5.3 log CFU g−1. The presence/absence of Cronobacter species was detected in 12 (18.8%) samples of: nuts (10 samples), and mixes (2 samples). The 12 strains of Cronobacter spp. included: C. sakazakii (3 strains), C. malonaticus (5), and C. turicensis (4). The results of this study contribute to the determination of the presence and species identification of Cronobacter spp. in products of plant origin intended for direct consumption. Full article
(This article belongs to the Special Issue Understanding the Roles of Bacterial Foodborne Pathogens in Global Food Safety)
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15 pages, 8344 KiB  
Review
A Scoping Review of West Nile Virus Seroprevalence Studies among African Equids
by Olaolu T. Olufemi, Marta Barba and Janet M. Daly
Pathogens 2021, 10(7), 899; https://doi.org/10.3390/pathogens10070899 - 15 Jul 2021
Cited by 2 | Viewed by 3869
Abstract
West Nile virus (WNV) is an emerging and re-emerging zoonotic flavivirus first identified in and endemic to Africa. The virus is transmitted between birds by biting mosquitoes, with equids and humans being incidental hosts. The majority of infected incidental hosts display no or [...] Read more.
West Nile virus (WNV) is an emerging and re-emerging zoonotic flavivirus first identified in and endemic to Africa. The virus is transmitted between birds by biting mosquitoes, with equids and humans being incidental hosts. The majority of infected incidental hosts display no or only mild clinical signs, but a fraction develop encephalitis. The aim of this scoping review was to identify and evaluate primary research on the presence of antibodies to WNV among African equids. Three bibliographic databases and the grey literature were searched. Of 283 articles identified, only 16 satisfied all the inclusion criteria. Data were collated on study design and outcomes. The overall seroprevalence reported ranged from 17.4 to 90.3%, with 1998 (35%) of the 5746 horses, donkeys and mules having screened positive for WNV antibodies. Several articles determined that seroprevalence increased significantly with age. Due to co-circulation of other flaviviruses in Africa, in the majority of studies that screened samples by ELISA, positive results were confirmed using a more specific neutralization test. However, only eight studies tested against other flaviviruses, including Potiskum, Uganda S, Wesselsbron and yellow fever virus in one, Japanese encephalitis and Usutu virus (USUV) in one, tick-borne encephalitis and USUV in one and USUV only in three. Equids are regarded as useful sentinel animals for WNV, but variation in study design poses challenges when trying to determine risk factors for, and trends in, WNV seroprevalence. Full article
(This article belongs to the Special Issue Emerging and Neglected Viruses and Zoonoses)
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13 pages, 2261 KiB  
Article
Variations in the Abortive HIV-1 RNA Hairpin Do Not Impede Viral Sensing and Innate Immune Responses
by Melissa Stunnenberg, John L. van Hamme, Atze T. Das, Ben Berkhout and Teunis B. H. Geijtenbeek
Pathogens 2021, 10(7), 897; https://doi.org/10.3390/pathogens10070897 - 15 Jul 2021
Cited by 1 | Viewed by 2472
Abstract
The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to antiviral immunity. While high variation [...] Read more.
The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to antiviral immunity. While high variation in the TAR RNA structure renders the virus replication-incompetent, effects on viral sensing remain unclear. Here, we investigated the role of TAR RNA structure and stability on viral sensing. TAR mutants with deletions in the TAR hairpin that enhanced thermodynamic stability increased antiviral responses. Strikingly, TAR mutants with lower stability due to destabilization of the TAR hairpin also increased antiviral responses without affecting pro-inflammatory responses. Moreover, mutations that affected the TAR RNA sequence also enhanced specific antiviral responses. Our data suggest that mutations in TAR of replication-incompetent viruses can still induce immune responses via viral sensors, hereby underscoring the robustness of HIV-1 RNA sensing mechanisms. Full article
(This article belongs to the Topic Novel Biomolecules Modulating Innate Immune Responses against Virus Infection)
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14 pages, 2325 KiB  
Article
West Nile Virus in Brazil
by Érica Azevedo Costa, Marta Giovanetti, Lilian Silva Catenacci, Vagner Fonseca, Flávia Figueira Aburjaile, Flávia L. L. Chalhoub, Joilson Xavier, Felipe Campos de Melo Iani, Marcelo Adriano da Cunha e Silva Vieira, Danielle Freitas Henriques, Daniele Barbosa de Almeida Medeiros, Maria Isabel Maldonado Coelho Guedes, Beatriz Senra Álvares da Silva Santos, Aila Solimar Gonçalves Silva, Renata de Pino Albuquerque Maranhão, Nieli Rodrigues da Costa Faria, Renata Farinelli de Siqueira, Tulio de Oliveira, Karina Ribeiro Leite Jardim Cavalcante, Noely Fabiana Oliveira de Moura, Alessandro Pecego Martins Romano, Carlos F. Campelo de Albuquerque, Lauro César Soares Feitosa, José Joffre Martins Bayeux, Raffaella Bertoni Cavalcanti Teixeira, Osmaikon Lisboa Lobato, Silvokleio da Costa Silva, Ana Maria Bispo de Filippis, Rivaldo Venâncio da Cunha, José Lourenço and Luiz Carlos Junior Alcantaraadd Show full author list remove Hide full author list
Pathogens 2021, 10(7), 896; https://doi.org/10.3390/pathogens10070896 - 15 Jul 2021
Cited by 14 | Viewed by 5916
Abstract
Background: West Nile virus (WNV) was first sequenced in Brazil in 2019, when it was isolated from a horse in the Espírito Santo state. Despite multiple studies reporting serological evidence suggestive of past circulation since 2004, WNV remains a low priority for surveillance [...] Read more.
Background: West Nile virus (WNV) was first sequenced in Brazil in 2019, when it was isolated from a horse in the Espírito Santo state. Despite multiple studies reporting serological evidence suggestive of past circulation since 2004, WNV remains a low priority for surveillance and public health, such that much is still unknown about its genomic diversity, evolution, and transmission in the country. Methods: A combination of diagnostic assays, nanopore sequencing, phylogenetic inference, and epidemiological modeling are here used to provide a holistic overview of what is known about WNV in Brazil. Results: We report new genetic evidence of WNV circulation in southern (Minas Gerais, São Paulo) and northeastern (Piauí) states isolated from equine red blood cells. A novel, climate-informed theoretical perspective of the potential transmission of WNV across the country highlights the state of Piauí as particularly relevant for WNV epidemiology in Brazil, although it does not reject possible circulation in other states. Conclusion: Our output demonstrates the scarceness of existing data, and that although there is sufficient evidence for the circulation and persistence of the virus, much is still unknown on its local evolution, epidemiology, and activity. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics with spill-over potential to humans. Full article
(This article belongs to the Special Issue West Nile Virus Infection)
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10 pages, 2385 KiB  
Article
Clinical, Radiological and Functional Characteristics of Pulmonary Diseases among HTLV-1 Infected Patients without Prior Active Tuberculosis Infection
by Rodrigo Cachay, Marcela Gil-Zacarias, Takashi Watanabe-Tejada, Alvaro Schwalb, Fernando Mejía, Oscar Gayoso and Eduardo Gotuzzo
Pathogens 2021, 10(7), 895; https://doi.org/10.3390/pathogens10070895 - 14 Jul 2021
Cited by 1 | Viewed by 1921
Abstract
The lifelong infection with the human T lymphotropic virus type 1 (HTLV-1) has been associated with a variety of clinical manifestations; one of the less-explored is HTLV-1-associated pulmonary disease. Imaging of lung damage caused by the HTLV-1 hyperinflammatory cascade can be similar to [...] Read more.
The lifelong infection with the human T lymphotropic virus type 1 (HTLV-1) has been associated with a variety of clinical manifestations; one of the less-explored is HTLV-1-associated pulmonary disease. Imaging of lung damage caused by the HTLV-1 hyperinflammatory cascade can be similar to sequelae from TB infection. Our study aims to describe the pulmonary lesions of HTLV-1-positive patients without past or current active TB and evaluate pulmonary function. We found that nine out of fourteen patients with no known TB disease history presented bronchiectasis, mainly found bilaterally while five presented pulmonary fibrosis. A normal pattern was found in most patients with a pulmonary functional test. Furthermore, there was no association between the PVL and the chest-CT scan findings, nor with spirometry results. However, the sample size was insufficient to conclude it. Full article
(This article belongs to the Special Issue Emerging and Neglected Viruses and Zoonoses)
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9 pages, 2981 KiB  
Article
The Autofluorescence Patterns of Acanthamoeba castellanii, Pseudomonas aeruginosa and Staphylococcus aureus: Effects of Antibiotics and Tetracaine
by Hari Kumar Peguda, Saabah B. Mahbub, Tashi Doma Sherpa, Dinesh Subedi, Abbas Habibalahi, Ayad G. Anwer, Zi Gu, Mark D. P. Willcox, Ewa M. Goldys and Nicole A. Carnt
Pathogens 2021, 10(7), 894; https://doi.org/10.3390/pathogens10070894 - 14 Jul 2021
Cited by 2 | Viewed by 3706
Abstract
Acanthamoeba Keratitis (AK) can lead to substantial vision loss and morbidity among contact lens wearers. Misdiagnosis or delayed diagnosis is a major factor contributing to poor outcomes of AK. This study aimed to assess the effect of two antibiotics and one anaesthetic drug [...] Read more.
Acanthamoeba Keratitis (AK) can lead to substantial vision loss and morbidity among contact lens wearers. Misdiagnosis or delayed diagnosis is a major factor contributing to poor outcomes of AK. This study aimed to assess the effect of two antibiotics and one anaesthetic drug used in the diagnosis and nonspecific management of keratitis on the autofluorescence patterns of Acanthamoeba and two common bacteria that may also cause keratitis. Acanthamoeba castellanii ATCC 30868, Pseudomonas aeruginosa ATCC 9027, and Staphylococcus aureus ATCC 6538 were grown then diluted in either PBS (bacteria) or ¼ strength Ringer’s solution (Acanthamoeba) to give final concentrations of 0.1 OD at 660 nm or 104 cells/mL. Cells were then treated with ciprofloxacin, tetracycline, tetracaine, or no treatment (naïve). Excitation–emission matrices (EEMs) were collected for each sample with excitation at 270–500 nm with increments in 5 nm steps and emission at 280–700 nm at 2 nm steps using a Fluoromax-4 spectrometer. The data were analysed using MATLAB software to produce smoothed color-coded images of the samples tested. Acanthamoeba exhibited a distinctive fluorescence pattern compared to bacteria. The addition of antibiotics and anaesthetic had variable effects on autofluorescence. Tetracaine altered the fluorescence of all three microorganisms, whereas tetracycline did not show any effect on the fluorescence. Ciprofloxacin produced changes to the fluorescence pattern for the bacteria, but not Acanthamoeba. Fluorescence spectroscopy was able to differentiate Acanthamoeba from P. aeruginosa and S. aureus in vitro. There is a need for further assessment of the fluorescence pattern for different strains of Acanthamoeba and bacteria. Additionally, analysis of the effects of anti-amoebic drugs on the fluorescence pattern of Acanthamoeba and bacteria would be prudent before in vivo testing of the fluorescence diagnostic approach in the animal models. Full article
(This article belongs to the Special Issue New Insights in Acanthamoeba)
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31 pages, 11282 KiB  
Systematic Review
Models for Studying the Distribution of Ticks and Tick-Borne Diseases in Animals: A Systematic Review and a Meta-Analysis with a Focus on Africa
by Olivier M. Zannou, Achille S. Ouedraogo, Abel S. Biguezoton, Emmanuel Abatih, Marco Coral-Almeida, Souaïbou Farougou, Kouassi Patrick Yao, Laetitia Lempereur and Claude Saegerman
Pathogens 2021, 10(7), 893; https://doi.org/10.3390/pathogens10070893 - 14 Jul 2021
Cited by 10 | Viewed by 4922
Abstract
Ticks and tick-borne diseases (TTBD) are constraints to the development of livestock and induce potential human health problems. The worldwide distribution of ticks is not homogenous. Some places are ecologically suitable for ticks but they are not introduced in these areas yet. The [...] Read more.
Ticks and tick-borne diseases (TTBD) are constraints to the development of livestock and induce potential human health problems. The worldwide distribution of ticks is not homogenous. Some places are ecologically suitable for ticks but they are not introduced in these areas yet. The absence or low density of hosts is a factor affecting the dissemination of the parasite. To understand the process of introduction and spread of TTBD in different areas, and forecast their presence, scientists developed different models (e.g., predictive models and explicative models). This study aimed to identify models developed by researchers to analyze the TTBD distribution and to assess the performance of these various models with a meta-analysis. A literature search was implemented with PRISMA protocol in two online databases (Scopus and PubMed). The selected articles were classified according to country, type of models and the objective of the modeling. Sensitivity, specificity and accuracy available data of these models were used to evaluate their performance using a meta-analysis. One hundred studies were identified in which seven tick genera were modeled, with Ixodes the most frequently modeled. Additionally, 13 genera of tick-borne pathogens were also modeled, with Borrelia the most frequently modeled. Twenty-three different models were identified and the most frequently used are the generalized linear model representing 26.67% and the maximum entropy model representing 24.17%. A focus on TTBD modeling in Africa showed that, respectively, genus Rhipicephalus and Theileria parva were the most modeled. A meta-analysis on the quality of 20 models revealed that maximum entropy, linear discriminant analysis, and the ecological niche factor analysis models had, respectively, the highest sensitivity, specificity, and area under the curve effect size among all the selected models. Modeling TTBD is highly relevant for predicting their distribution and preventing their adverse effect on animal and human health and the economy. Related results of such analyses are useful to build prevention and/or control programs by veterinary and public health authorities. Full article
(This article belongs to the Special Issue Emerging Vector-Borne and Zoonotic Diseases)
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13 pages, 1497 KiB  
Article
Tularemia Outbreaks in Spain from 2007 to 2020 in Humans and Domestic and Wild Animals
by Olga Mínguez-González, César-Bernardo Gutiérrez-Martín, María del Carmen Martínez-Nistal, María del Rosario Esquivel-García, José-Ignacio Gómez-Campillo, Jesús-Ángel Collazos-Martínez, Luis-Miguel Fernández-Calle, Cristina Ruiz-Sopeña, Sonia Tamames-Gómez, Sonia Martínez-Martínez, Constantino Caminero-Saldaña, Marta Hernández, David Rodríguez-Lázaro and Elías-Fernando Rodríguez-Ferri
Pathogens 2021, 10(7), 892; https://doi.org/10.3390/pathogens10070892 - 14 Jul 2021
Cited by 9 | Viewed by 2700
Abstract
In this study, tularemia outbreaks associated with humans and several domestic and wild animals (Iberian hares, wild rabbits, voles, mice, grey shrews, sheep, dogs, foxes, wolves, ticks, and river crayfish) are reported in Spain from 2007 to 2020. Special attention was paid to [...] Read more.
In this study, tularemia outbreaks associated with humans and several domestic and wild animals (Iberian hares, wild rabbits, voles, mice, grey shrews, sheep, dogs, foxes, wolves, ticks, and river crayfish) are reported in Spain from 2007 to 2020. Special attention was paid to the outbreaks in humans in 2007–2009 and 2014–2015, when the most important waves occurred. Moreover, positive rates of tularemia in lagomorphs were detected in 2007–2010, followed by negative results in 2011–2013, before again returning to positive rates in 2014 and in 2017 and in 2019–2020. Lagomorphs role in spreading Francisella tularensis in the epidemiological chain could not be discarded. F. tularensis is described for the first time infecting the shrew Crocidura russula worldwide, and it is also reported for the first time infecting wild rabbits (Oryctolagus cuniculus) in Spain. Serological positives higher than 0.4% were seen for sheep only from 2007–2009 and again in 2019, while serological rates greater than 1% were revealed in dogs in 2007–2008 and in wild canids in 2016. F. tularensis were detected in ticks in 2009, 2014–2015, 2017, and 2019. Lastly, negative results were achieved for river crayfish and also in environmental water samples from 2007 to 2020. Full article
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12 pages, 1940 KiB  
Article
A Comparison of Virulence of Three Porcine Circovirus Type 2 (PCV2) Genotypes (a, b, and d) in Pigs Singularly Inoculated with PCV2 and Dually Inoculated with PCV2 and Porcine Reproductive and Respiratory Syndrome Virus
by Jeongmin Suh, Taehwan Oh, Keehwan Park, Siyeon Yang, Hyejean Cho and Chanhee Chae
Pathogens 2021, 10(7), 891; https://doi.org/10.3390/pathogens10070891 - 14 Jul 2021
Cited by 6 | Viewed by 2531
Abstract
The aim of this study was to compare the virulence of porcine circovirus type 2 (PCV2) genotypes in dually inoculated pigs with both three genotypes (a, b, and d) of PCV2 and porcine reproductive and respiratory syndrome virus-2 (PRRSV-2) versus pigs singularly inoculated [...] Read more.
The aim of this study was to compare the virulence of porcine circovirus type 2 (PCV2) genotypes in dually inoculated pigs with both three genotypes (a, b, and d) of PCV2 and porcine reproductive and respiratory syndrome virus-2 (PRRSV-2) versus pigs singularly inoculated with the same three PCV2 genotypes (a, b, and d). Differences in this comparison were found in PCV2 viremia levels, lung and lymphoid lesion severity, and the amount of PCV2 antigen within the lymphoid lesions. Regardless of PCV2 genotypes, pigs that were dually inoculated with PCV2/PRRSV had significantly higher clinical scores, less average daily weight gain, higher levels of PCV2 viremia, and more severe lug and lymphoid lesions compared to pigs singularly inoculated with PCV2. Among the dually infected pig groups, pigs infected with PCV2d/PRRSV-2 had significantly higher levels of PCV2 viremia, more severe lung and lymphoid lesions, and more PCV2-positive cells within lymphoid lesions compared to pigs dually inoculated with PCV2a/PRRSV-2 and PCV2b/PRRSV-2. The results of this study demonstrated significant differences in the virulence among dual inoculation of PCV2a/PRRSV-2, PCV2b/PRRSV-2, and PCV2d/PRRSV-2. A significant difference in the virulence among PCV2a, PCV2b, and PCV2d single-inoculated pig groups was not found with respect to the levels of PCV2 viremia and production of PCV2-associated lymphoid lesions. Full article
(This article belongs to the Special Issue The Advanced Research on Porcine Circovirus)
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6 pages, 1013 KiB  
Brief Report
Treatment with Micafungin in a Preterm Neonate with an Invasive Candida parapsilosis Infection after a Severe Terlipressin-Induced Skin Necrosis
by Domenico Umberto De Rose, Fiammetta Piersigilli, Bianca Maria Goffredo, Olivier Danhaive, Andrea Dotta and Cinzia Auriti
Pathogens 2021, 10(7), 890; https://doi.org/10.3390/pathogens10070890 - 13 Jul 2021
Cited by 1 | Viewed by 2379
Abstract
Candida parapsilosis infections are increasingly reported in preterm neonates, but the optimal treatment remains uncertain. We report the clinical history of an extremely preterm neonate, who developed a devastating skin necrosis due to terlipressin administration, with subsequent superinfection by Candida parapsilosis. The [...] Read more.
Candida parapsilosis infections are increasingly reported in preterm neonates, but the optimal treatment remains uncertain. We report the clinical history of an extremely preterm neonate, who developed a devastating skin necrosis due to terlipressin administration, with subsequent superinfection by Candida parapsilosis. The infant underwent multiple curettages and skin grafts to resolve skin lesions and was treated with systemic micafungin administration at a high dose (8 mg/kg/day), with resolution of the fungal infection. Full article
(This article belongs to the Section Fungal Pathogens)
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22 pages, 18705 KiB  
Review
Zoonotic Malaria: Non-Laverania Plasmodium Biology and Invasion Mechanisms
by Jing-Wen Hang, Farhana Tukijan, Erica-Qian-Hui Lee, Shifana Raja Abdeen, Yaw Aniweh and Benoit Malleret
Pathogens 2021, 10(7), 889; https://doi.org/10.3390/pathogens10070889 - 13 Jul 2021
Cited by 8 | Viewed by 13869
Abstract
Malaria, which is caused by Plasmodium parasites through Anopheles mosquito transmission, remains one of the most life-threatening diseases affecting hundreds of millions of people worldwide every year. Plasmodium vivax, which accounts for the majority of cases of recurring malaria caused by the [...] Read more.
Malaria, which is caused by Plasmodium parasites through Anopheles mosquito transmission, remains one of the most life-threatening diseases affecting hundreds of millions of people worldwide every year. Plasmodium vivax, which accounts for the majority of cases of recurring malaria caused by the Plasmodium (non-Laverania) subgenus, is an ancient and continuing zoonosis originating from monkey hosts probably outside Africa. The emergence of other zoonotic malarias (P. knowlesi, P. cynomolgi, and P. simium) further highlights the seriousness of the disease. The severity of this epidemic disease is dependent on many factors, including the parasite characteristics, host-parasite interactions, and the pathology of the infection. Successful infection depends on the ability of the parasite to invade the host; however, little is known about the parasite invasion biology and mechanisms. The lack of this information adds to the challenges to malaria control and elimination, hence enhancing the potential for continuation of this zoonosis. Here, we review the literature describing the characteristics, distribution, and genome details of the parasites, as well as host specificity, host-parasite interactions, and parasite pathology. This information will provide the basis of a greater understanding of the epidemiology and pathogenesis of malaria to support future development of strategies for the control and prevention of this zoonotic infection. Full article
(This article belongs to the Special Issue Advances in Human Pathogens Infections)
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12 pages, 280 KiB  
Article
Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM
by Francesca Rollo, Alessandra Latini, Massimo Giuliani, Amalia Giglio, Maria Gabriella Donà and Maria Benevolo
Pathogens 2021, 10(7), 888; https://doi.org/10.3390/pathogens10070888 - 13 Jul 2021
Viewed by 1859
Abstract
Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 [...] Read more.
Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM. Full article
(This article belongs to the Special Issue HPV Molecular Diagnostics: Laboratory, Research, and Clinical Aspects)
15 pages, 1192 KiB  
Review
Modulation of Neuroinflammation by the Gut Microbiota in Prion and Prion-Like Diseases
by Josephine Trichka and Wen-Quan Zou
Pathogens 2021, 10(7), 887; https://doi.org/10.3390/pathogens10070887 - 13 Jul 2021
Cited by 7 | Viewed by 4402
Abstract
The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as [...] Read more.
The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as leukocyte reaction to aggregation and accumulation of proteins in the CNS, are the primary mechanisms by which neuroinflammation is initiated. While processes local to the CNS may instigate neurodegenerative disease, the existence or dysregulation of systemic homeostasis can also serve to improve or worsen CNS pathologies, respectively. One fundamental component of systemic homeostasis is the gut microbiota, which communicates with the CNS via microbial metabolite production, the peripheral nervous system, and regulation of tryptophan metabolism. Over the past 10–15 years, research focused on the microbiota–gut–brain axis has culminated in the discovery that dysbiosis, or an imbalance between commensal and pathogenic gut bacteria, can promote CNS pathologies. Conversely, a properly regulated and well-balanced microbiome supports CNS homeostasis and reduces the incidence and extent of pathogenic neuroinflammation. This review will discuss the role of the gut microbiota in exacerbating or alleviating neuroinflammation in neurodegenerative diseases, and potential microbiota-based therapeutic approaches to reduce pathology in diseased states. Full article
(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)
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16 pages, 3396 KiB  
Article
Antistaphylococcal Activity of the FtsZ Inhibitor C109
by Gabriele Trespidi, Viola Camilla Scoffone, Giulia Barbieri, Federica Marchesini, Aseel Abualshaar, Tom Coenye, Francesca Ungaro, Vadim Makarov, Roberta Migliavacca, Edda De Rossi and Silvia Buroni
Pathogens 2021, 10(7), 886; https://doi.org/10.3390/pathogens10070886 - 13 Jul 2021
Cited by 5 | Viewed by 2557
Abstract
Staphylococcus aureus infections represent a great concern due to their versatility and involvement in different types of diseases. The shortage of available clinical options, especially to treat multiresistant strains, makes the discovery of new effective compounds essential. Here we describe the activity of [...] Read more.
Staphylococcus aureus infections represent a great concern due to their versatility and involvement in different types of diseases. The shortage of available clinical options, especially to treat multiresistant strains, makes the discovery of new effective compounds essential. Here we describe the activity of the previously described cell division inhibitor C109 against methicillin-sensitive and -resistant S. aureus strains. Antibiofilm activity was assessed using microtiter plates, confocal microscopy, and in an in vitro biofilm wound model. The ability of C109 to block FtsZ GTPase activity and polymerization was tested in vitro. Altogether, the results show that the FtsZ inhibitor C109 has activity against a wide range of S. aureus strains and support its use as an antistaphylococcal compound. Full article
(This article belongs to the Special Issue Staphylococcus Infections in Humans and Animals)
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8 pages, 592 KiB  
Communication
The Emergence of Rift Valley Fever in Gedaref State Urges the Need for a Cross-Border One Health Strategy and Enforcement of the International Health Regulations
by Ayman Ahmed, Iman Mahmoud, Mawahib Eldigail, Rehab M. Elhassan and Scott C. Weaver
Pathogens 2021, 10(7), 885; https://doi.org/10.3390/pathogens10070885 - 13 Jul 2021
Cited by 17 | Viewed by 3033
Abstract
This study investigated the causative agent of a haemorrhagic fever epidemic in Gedaref state, south-east Sudan. Six cases of febrile illness with haemorrhagic manifestations presented at outpatient health-clinics. Blood samples were collected from the patients and shipped to Khartoum where they were tested [...] Read more.
This study investigated the causative agent of a haemorrhagic fever epidemic in Gedaref state, south-east Sudan. Six cases of febrile illness with haemorrhagic manifestations presented at outpatient health-clinics. Blood samples were collected from the patients and shipped to Khartoum where they were tested for dengue virus (DENV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV) using real-time qPCR. Fifty percent (3/6) of them tested positive for RVFV and neither DENV or CHIKV was detected. All patients were males between 20 and 48 years old who had no history of recent travel. This finding describes the first emergence of RVFV in Gedaref state. Considering that the state hosts a major market of livestock, and it has one of the largest-seasonal open pastures in the country that is usually flooded with herds from the neighbouring states and countries during the rainy season, this emergence could represent a major threat to public health in the region and countries importing animals and/or animal products from east Africa. Therefore, we urge the policymakers of the health and animal resources sectors to implement a one health strategy with a well-established early warning surveillance and response system to prevent the establishment of the disease in the area. Full article
(This article belongs to the Section Emerging Pathogens)
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12 pages, 1996 KiB  
Article
The Pathogens Spillover and Incidence Correlation in Bumblebees and Honeybees in Slovenia
by Metka Pislak Ocepek, Ivan Toplak, Urška Zajc and Danilo Bevk
Pathogens 2021, 10(7), 884; https://doi.org/10.3390/pathogens10070884 - 12 Jul 2021
Cited by 13 | Viewed by 2840
Abstract
Slovenia has a long tradition of beekeeping and a high density of honeybee colonies, but less is known about bumblebees and their pathogens. Therefore, a study was conducted to define the incidence and prevalence of pathogens in bumblebees and to determine whether there [...] Read more.
Slovenia has a long tradition of beekeeping and a high density of honeybee colonies, but less is known about bumblebees and their pathogens. Therefore, a study was conducted to define the incidence and prevalence of pathogens in bumblebees and to determine whether there are links between infections in bumblebees and honeybees. In 2017 and 2018, clinically healthy workers of bumblebees (Bombus spp.) and honeybees (Apis mellifera) were collected on flowers at four different locations in Slovenia. In addition, bumblebee queens were also collected in 2018. Several pathogens were detected in the bumblebee workers using PCR and RT-PCR methods: 8.8% on acute bee paralysis virus (ABPV), 58.5% on black queen cell virus (BQCV), 6.8% on deformed wing virus (DWV), 24.5% on sacbrood bee virus (SBV), 15.6% on Lake Sinai virus (LSV), 16.3% on Nosema bombi, 8.2% on Nosema ceranae, 15.0% on Apicystis bombi and 17.0% on Crithidia bombi. In bumblebee queens, only the presence of BQCV, A. bombi and C. bombi was detected with 73.3, 26.3 and 33.3% positive samples, respectively. This study confirmed that several pathogens are regularly detected in both bumblebees and honeybees. Further studies on the pathogen transmission routes are required. Full article
(This article belongs to the Special Issue Infection in Honey Bees: Host–Pathogen Interaction and Spillover)
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