Pathogens

Open AccessArticle

Development of In Vitro Assays with the Canine Hookworm Uncinaria stenocephala and Assessment of Natural Plant Products for Anti-Parasitic Activity

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Pathogens 2023, 12(4), 536; https://doi.org/10.3390/pathogens12040536 (registering DOI) - 29 Mar 2023

Abstract

Enteric helminth infection is an increasing concern in companion animals due to reports of resistance to commonly used anthelmintic drugs. Thus, the assessment of new therapeutic options such as bioactive dietary additives is of high importance. Here, we adapted egg hatch, larval migration, [...] Read more.

Enteric helminth infection is an increasing concern in companion animals due to reports of resistance to commonly used anthelmintic drugs. Thus, the assessment of new therapeutic options such as bioactive dietary additives is of high importance. Here, we adapted egg hatch, larval migration, and larval motility assays to screen extracts of several natural ingredients against the canine hookworm Uncinaria stenocephala, a prevalent parasite of dogs in northern Europe. Egg hatch and larval migration assays were established showing that the anthelmintic drugs levamisole and albendazole had strong anti-parasitic activity against U. stenocephala, validating the use of these assays for the assessment of novel anti-parasitic substances. Subsequently, we identified that extracts from the seaweed Saccharina latissima, but not extracts from grape seed or chicory, significantly inhibited both hatching and larval migration. Finally, we showed that α-linolenic acid, a putative anti-parasitic compound from S. latissima, also exhibited anti-parasitic activity. Collectively, our results established a platform for the screening for anthelmintic resistance or novel drug candidates against U. stenocephala and highlighted the potential use of seaweed extracts as a functional food component to help control hookworm infection in dogs. Full article

(This article belongs to the Special Issue Parasites: Epidemiology, Treatment and Control)

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Open AccessArticle

Novel Identification of the Collection of Pathogenic Fungal Species Verticillium with the Development of Species-Specific SSR Markers

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Pathogens 2023, 12(4), 535; https://doi.org/10.3390/pathogens12040535 (registering DOI) - 29 Mar 2023

Abstract

The genus Verticillium is a group of ascomycete fungi that includes several pathogenic plant species. In 2011, a new taxonomic classification, proposed by Inderbitzin and coworkers (2011), re-defined the genus as Verticillium sensu stricto. The objective of our study was the re-classification of [...] Read more.

The genus Verticillium is a group of ascomycete fungi that includes several pathogenic plant species. In 2011, a new taxonomic classification, proposed by Inderbitzin and coworkers (2011), re-defined the genus as Verticillium sensu stricto. The objective of our study was the re-classification of the fungal species held in the culture collection in the Slovenian Institute of Hop Research and Brewing in accordance with the newly established taxonomy. With the PCR marker system proposed by Inderbitzin and coworkers in 2011, we re-classified 88 Verticillium isolates out of the 105 samples that are held in the institute’s bank, which were obtained from different geographic locations in Europe, North America, and Japan, and from different host plants, including alfalfa, cotton, hop, olive, potato, and tomato. However, the PCR marker for the V. dahliae identification proved to be less specific, and it resulted in the positive amplification of Gibellulopsis nigrescens, V. isaacii, and V. longisporum. To enable the accurate distinction of the fungi, the SSR and LAMP markers were added to the analyses. The 12 newly identified SSR markers, which were used in simplex PCR reactions or in combination, enabled the accurate identification of all included Verticillium isolates and could potentially be used as biomarkers for rapid and easy species identification. Full article

(This article belongs to the Special Issue Recent Advances on Pathogenomics and Effectoromics of Verticillium Species)

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Open AccessArticle

Toll-like Receptor-9 (TLR-9) Signaling Is Crucial for Inducing Protective Immunity following Immunization with Genetically Modified Live Attenuated Leishmania Parasites

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Pathogens 2023, 12(4), 534; https://doi.org/10.3390/pathogens12040534 (registering DOI) - 29 Mar 2023

Abstract

No human vaccine is available for visceral leishmaniasis (VL). Live attenuated centrin gene-deleted L. donovani (LdCen^−/−) parasite vaccine has been shown to induce robust innate immunity and provide protection in animal models. Toll-like receptors (TLRs) are expressed in innate immune [...] Read more.

No human vaccine is available for visceral leishmaniasis (VL). Live attenuated centrin gene-deleted L. donovani (LdCen^−/−) parasite vaccine has been shown to induce robust innate immunity and provide protection in animal models. Toll-like receptors (TLRs) are expressed in innate immune cells and are essential for the early stages of Leishmania infection. Among TLRs, TLR-9 signaling has been reported to induce host protection during Leishmania infection. Importantly, TLR-9 ligands have been used as immune enhancers for non-live vaccination strategies against leishmaniasis. However, the function of TLR-9 in the generation of a protective immune response in live attenuated Leishmania vaccines remains unknown. In this study, we investigated the function of TLR-9 during LdCen^−/− infection and found that it increased the expression of TLR-9 on DCs and macrophages from ear-draining lymph nodes and spleen. The increase in TLR-9 expression resulted in changes in downstream signaling in DCs mediated through signaling protein myeloid differentiation primary response 88 (MyD88), resulting in activation and nuclear translocation of nuclear factor-κB (NF-κB). This process resulted in an increase in the DC’s proinflammatory response, activation, and DC-mediated CD4⁺T cell proliferation. Further, LdCen^−/− immunization in TLR-9^−/− mice resulted in a significant loss of protective immunity. Thus, LdCen^−/− vaccine naturally activates the TLR-9 signaling pathway to elicit protective immunity against virulent L. donovani challenge. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David)

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Open AccessBrief Report

Rapid Identification of ASFV, CSFV and FMDV from Mongolian Outbreaks with MinION Short Amplicon Sequencing

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Dashzeveg Bold

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Jayme A. Souza-Neto

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Delgerzul Gombo-Ochir

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Natasha N. Gaudreault

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Pathogens 2023, 12(4), 533; https://doi.org/10.3390/pathogens12040533 (registering DOI) - 29 Mar 2023

Abstract

African swine fever virus (ASFV), classical swine fever virus (CSFV), and foot-and-mouth disease virus (FMDV) cause important transboundary animal diseases (TADs) that have a significant economic impact. The rapid and unequivocal identification of these pathogens and distinction from other animal diseases based on [...] Read more.

African swine fever virus (ASFV), classical swine fever virus (CSFV), and foot-and-mouth disease virus (FMDV) cause important transboundary animal diseases (TADs) that have a significant economic impact. The rapid and unequivocal identification of these pathogens and distinction from other animal diseases based on clinical symptoms in the field is difficult. Nevertheless, early pathogen detection is critical in limiting their spread and impact as is the availability of a reliable, rapid, and cost-effective diagnostic test. The purpose of this study was to evaluate the feasibility to identify ASFV, CSFV, and FMDV in field samples using next generation sequencing of short PCR products as a point-of-care diagnostic. We isolated nucleic acids from tissue samples of animals in Mongolia that were infected with ASFV (2019), CSFV (2015), or FMDV (2018), and performed conventional (RT-) PCR using primers recommended by the Terrestrial Animal Health Code of the World Organization for Animal Health (WOAH). The (RT-) PCR products were then sequenced in Mongolia using the MinION nanopore portable sequencer. The resulting sequencing reads successfully identified the respective pathogens that exhibited 91–100% nucleic acid similarity to the reference strains. Phylogenetic analyses suggest that the Mongolian virus isolates are closely related to other isolates circulating in the same geographic region. Based on our results, sequencing short fragments derived by conventional (RT-) PCR is a reliable approach for rapid point-of-care diagnostics for ASFV, CSFV, and FMDV even in low-resource countries. Full article

(This article belongs to the Special Issue Molecular Detection and Characterisation of Viral Pathogens)

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Open AccessComment

Coronavirus Disease 2019 and Primary Antibody Deficiencies. Comment on Milota et al. Clinical Outcome of Coronavirus Disease 2019 in Patients with Primary Antibody Deficiencies. Pathogens 2023, 12, 109

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Öner Özdemir

Pathogens 2023, 12(4), 532; https://doi.org/10.3390/pathogens12040532 (registering DOI) - 29 Mar 2023

Abstract

We have read the article titled ‘Clinical Outcome of Coronavirus Disease 2019 in Patients with Primary Antibody Deficiencies’ by Milota et al. with great interestl [...] Full article

Open AccessReview

Understanding Animal-Plant-Parasite Interactions to Improve the Management of Gastrointestinal Nematodes in Grazing Ruminants

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Patrizia Ana Bricarello

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Cibele Longo

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Raquel Abdallah da Rocha

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Maria José Hötzel

Pathogens 2023, 12(4), 531; https://doi.org/10.3390/pathogens12040531 (registering DOI) - 29 Mar 2023

Abstract

Grazing systems have great potential to promote animal welfare by allowing animals to express natural behaviours, but they also present risks to the animals. Diseases caused by gastrointestinal nematodes are some of the most important causes of poor ruminant health and welfare in [...] Read more.

Grazing systems have great potential to promote animal welfare by allowing animals to express natural behaviours, but they also present risks to the animals. Diseases caused by gastrointestinal nematodes are some of the most important causes of poor ruminant health and welfare in grazing systems and cause important economic losses. Reduced growth, health, reproduction and fitness, and negative affective states that indicate suffering are some of the negative effects on welfare in animals infected by gastrointestinal nematode parasitism. Conventional forms of control are based on anthelmintics, but their growing inefficiency due to resistance to many drugs, their potential for contamination of soil and products, and negative public opinion indicate an urgency to seek alternatives. We can learn to deal with these challenges by observing biological aspects of the parasite and the host’s behaviour to develop managements that have a multidimensional view that vary in time and space. Improving animal welfare in the context of the parasitic challenge in grazing systems should be seen as a priority to ensure the sustainability of livestock production. Among the measures to control gastrointestinal nematodes and increase animal welfare in grazing systems are the management and decontamination of pastures, offering multispecies pastures, and grazing strategies such as co-grazing with other species that have different grazing behaviours, rotational grazing with short grazing periods, and improved nutrition. Genetic selection to improve herd or flock parasite resistance to gastrointestinal nematode infection may also be incorporated into a holistic control plan, aiming at a substantial reduction in the use of anthelmintics and endectocides to make grazing systems more sustainable. Full article

(This article belongs to the Special Issue Advances in the Control of the Helminthosis in Domestic Animals)

Open AccessCase Report

A Rare Case of Strongyloides stercoralis Hyperinfection in a Diabetic Patient from Romania—Case Report and Review of the Literature

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Carmen Costache

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Ioana Alina Colosi

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Vlad Sever Neculicioiu

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Pathogens 2023, 12(4), 530; https://doi.org/10.3390/pathogens12040530 - 29 Mar 2023

Abstract

Severe cases of strongyloidiasis are most often associated with multiple causes of immune suppression, such as corticoid treatment and HTLV (human T-lymphotropic virus) coinfection. Diabetes is not traditionally considered a risk factor for the development of severe strongyloidiasis. We report a rare case [...] Read more.

Severe cases of strongyloidiasis are most often associated with multiple causes of immune suppression, such as corticoid treatment and HTLV (human T-lymphotropic virus) coinfection. Diabetes is not traditionally considered a risk factor for the development of severe strongyloidiasis. We report a rare case of autochthonous severe strongyloidiasis in Romania, a European country with a temperate climate. A 71-year-old patient with no prior travel history was admitted with multiple gastrointestinal complaints and recent weight loss. CT (computed tomography) scans indicated duodenal wall thickening, and duodenal endoscopy evidenced mucosal inflammation, ulcerations and partial duodenal obstruction at D4. Microscopic examination of stool samples and biopsy specimens from the gastric and duodenal mucosa revealed an increased larval burden characteristic of Strongyloides stercoralis hyperinfection. Sequential treatment with albendazole and ivermectin achieved parasitological cure and complete recovery. The novelty of our case stems from the scarcity of severe strongyloidiasis cases reported in Europe and especially in Romania, the absence of other risk factors in our patient aside from diabetes, the involvement of the gastric mucosa and the rare presentation as partial duodenal obstruction. This case highlights the importance of considering strongyloidiasis as a differential diagnosis, even in temperate climates where cases are sporadic, in cases in which immune suppression is not evident and in the absence of eosinophilia. The case is presented in the context of the first literature review examining the relationship between severe strongyloidiasis and diabetes, emphasizing diabetes as a possible risk factor for severe strongyloidiasis. Full article

(This article belongs to the Special Issue Novel Insights into Parasitic Infections and Diseases)

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Open AccessArticle

Study of the Genetic Expression of Antiretroviral Restriction Factors and Acute Phase Proteins in Cattle Infected with Bovine Leukemia Virus

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Ana S. González-Méndez

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Jorge L. Tórtora Pérez

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Edith Rojas-Anaya

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Hugo Ramírez Álvarez

Pathogens 2023, 12(4), 529; https://doi.org/10.3390/pathogens12040529 - 29 Mar 2023

Abstract

The goal of this study was to analyze the genetic expression of antiretroviral restriction factors (ARF) and acute phase proteins (APP), as well as their correlation with proviral and viral loads in cattle with aleukemic (AL) and persistent lymphocytosis (PL). Complete blood samples [...] Read more.

The goal of this study was to analyze the genetic expression of antiretroviral restriction factors (ARF) and acute phase proteins (APP), as well as their correlation with proviral and viral loads in cattle with aleukemic (AL) and persistent lymphocytosis (PL). Complete blood samples were collected from a herd of dairy cows, and we extracted genetic material from peripheral blood leukocytes. Absolute quantification of the expression of ARF (APOBEC-Z1, Z2, and Z3; HEXIM-1, HEXIM-2, and BST2) and APP (haptoglobin (HP), and serum amyloid A (SAA)) was performed by qPCR. Statistical significance was observed in the expression of APOBEC-Z3 in BLV-infected animals. We only found positive correlations with a strong expression of the ARF genes in the AL group. The participation of APOBEC (Z1 and Z3), HEXIM-1, and HEXIM-2 was more frequently identified in BLV-infected animals. HEXIM-2 showed active gene expression in the AL group. Although the expression of ARF in early stages of infection (AL) maintains an important participation, in late stages (PL) it seems to have little relevance. Full article

(This article belongs to the Collection Bovine Leukemia Virus Infection)

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Open AccessCommunication

Detection of Babesia conradae in Coyotes (Canis latrans) and Coyote-Hunting Greyhound Dogs (Canis familiaris)

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Haley Furman

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Ruth C. Scimeca

Pathogens 2023, 12(4), 528; https://doi.org/10.3390/pathogens12040528 - 29 Mar 2023

Abstract

Babesia conradae is a small piroplasm previously detected in coyote-hunting Greyhound dogs in California and Oklahoma. In dogs, B. conradae causes clinical signs similar to other tick-borne illnesses, and if not treated it can lead to acute kidney injury and other life-threating complications. [...] Read more.

Babesia conradae is a small piroplasm previously detected in coyote-hunting Greyhound dogs in California and Oklahoma. In dogs, B. conradae causes clinical signs similar to other tick-borne illnesses, and if not treated it can lead to acute kidney injury and other life-threating complications. To date, the life cycle of this apicomplexan parasite has not been fully described, but suggestions of direct contact or tick transmission have been proposed. The purpose of this study was to test coyote tissue samples from coyotes hunted by Greyhound dogs with a history of B. conradae infection to determine if this parasite is present in the coyote population in Northwestern Oklahoma. The analyzed tissue samples included liver, lung and tongue samples collected by hunters. DNA was isolated from these tissues and assessed by RT-PCR of the 18S rRNA and PCR of the COX1 genes for B. conradae. A total of 66 dogs and 38 coyotes were tested, and the results demonstrated the presence of B. conradae DNA in 21 dogs (31.8%) and 4 coyotes (10.5%). These results indicate that B. conradae is present in the dog and coyote population from the same area and that direct contact with coyotes may increase the risk of infection in dogs. Further studies are required to test possible modes of transmission, including direct bite, tick or vertical transmission. Full article

(This article belongs to the Special Issue Ticks & Piroplasms: Updates and Emerging Challenges)

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Open AccessArticle

HGPRT and PNP: Recombinant Enzymes from Schistosoma mansoni and Their Role in Immunotherapy during Experimental Murine Schistosomiasis

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Bruna Dias de Lima Fragelli

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Ana Carolina Maragno Fattori

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Elisandra de Almeida Montija

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Joice Margareth de Almeida Rodolpho

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Cynthia Aparecida de Castro

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Krissia Franco de Godoy

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Humberto D’Muniz Pereira

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Fernanda de Freitas Anibal

Pathogens 2023, 12(4), 527; https://doi.org/10.3390/pathogens12040527 - 29 Mar 2023

Abstract

Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus Schistosoma sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying aspect, since [...] Read more.

Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus Schistosoma sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying aspect, since there is loss of sensitivity of the parasite to the medication recommended by the World Health Organization, Praziquantel. The present study evaluated the effects of the recombinant enzymes of S. mansoni Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), Purine Nucleoside Phosphorylase (PNP) and the MIX of both enzymes in the immunotherapy of schistosomiasis in murine model. These enzymes are part of the purine salvage pathway, the only metabolic pathway present in the parasite for this purpose, being essential for the synthesis of DNA and RNA. Female mice of Swiss and BALB/c strains were infected with cercariae and treated, intraperitoneally, with three doses of 100 µg of enzymes. After the immunotherapy, the eggs and adult worms were counted in the feces; the number of eosinophils from the fluid in the peritoneal cavity and peripheral blood was observed; and the quantification of the cytokine IL-4 and the production of antibodies IgE was analyzed. The evaluation of the number of granulomas and collagen deposition via histological slides of the liver was performed. The results demonstrate that immunotherapy with the enzyme HGPRT seems to stimulate the production of IL-4 and promoted a significant reduction of granulomas in the liver in treated animals. The treatment with the enzyme PNP and the MIX was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine, to reduce the number of eggs in the feces and to negatively modulate the number of eosinophils. Therefore, immunotherapy with the recombinant enzymes of S. mansoni HGPRT and PNP might contribute to the control and reduction of the pathophysiological aspects of schistosomiasis, helping to decrease the morbidity associated with the infection in murine model. Full article

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Open AccessFeature PaperArticle

Evaluating the Diagnostic Potential of Chorismate Mutase Poly-Clonal Peptide Antibody for the Acanthamoeba Keratitis in an Animal Model

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Pathogens 2023, 12(4), 526; https://doi.org/10.3390/pathogens12040526 - 28 Mar 2023

Abstract

Acanthamoeba spp. is the causative agent of Acanthamoeba keratitis (AK), a vision-threatening parasitic disease whose primary risk factor has been attributed to poor contact lens hygiene. Unfortunately, differential diagnosis of AK is challenging as the clinical manifestations for AK are similar to those [...] Read more.

Acanthamoeba spp. is the causative agent of Acanthamoeba keratitis (AK), a vision-threatening parasitic disease whose primary risk factor has been attributed to poor contact lens hygiene. Unfortunately, differential diagnosis of AK is challenging as the clinical manifestations for AK are similar to those of bacterial, fungal, or even viral keratitis. Since delayed AK diagnosis can incur permanent vision impairment, a rapid and sensitive diagnostic method is urgently needed. Here, the diagnostic potential of polyclonal antibodies targeting the chorismate mutase (CM) of Acanthamoeba spp. was evaluated in AK animal models. CM antibody specificity against Acanthamoeba trophozoites and cysts was confirmed by immunocytochemistry after co-culturing Acanthamoeba with Fusarium solani, Pseudomonas aeruginosa, and Staphylococcus aureus, and human corneal epithelial (HCE) cells. Enzyme-linked immunosorbent assay (ELISA) was performed using CM-specific immune sera raised in rabbits, which demonstrated that the antibodies specifically interacted with the Acanthamoeba trophozoites and cysts in a dose-dependent manner. To evaluate the diagnostic potential of the CM antibody, AK animal models were established by incubating contact lenses with an inoculum containing A. castellanii trophozoites and subsequently overlaying these lenses onto the corneas of BALB/c mice for 7 and 21 days. The CM antibody specifically detected Acanthamoeba antigens in the murine lacrimal and eyeball tissue lysates at both time points. Our findings underscore the importance of antibody-based AK diagnosis, which could enable early and differential AK diagnosis in clinical settings. Full article

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Open AccessArticle

Geographical, Temporal and Host-Species Distribution of Potentially Human-Pathogenic Group B Streptococcus in Aquaculture Species in Southeast Asia

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Pathogens 2023, 12(4), 525; https://doi.org/10.3390/pathogens12040525 - 28 Mar 2023

Abstract

Group B Streptococcus (GBS) is a major pathogen of humans and aquatic species. Fish have recently been recognized as the source of severe invasive foodborne GBS disease, caused by sequence type (ST) 283, in otherwise healthy adults in Southeast Asia. Thailand and Vietnam [...] Read more.

Group B Streptococcus (GBS) is a major pathogen of humans and aquatic species. Fish have recently been recognized as the source of severe invasive foodborne GBS disease, caused by sequence type (ST) 283, in otherwise healthy adults in Southeast Asia. Thailand and Vietnam are among the major aquaculture producers in Southeast Asia, with GBS disease reported in fish as well as frogs in both countries. Still, the distribution of potentially human-pathogenic GBS in aquaculture species is poorly known. Using 35 GBS isolates from aquatic species in Thailand collected from 2007 to 2019 and 43 isolates from tilapia collected in Vietnam in 2018 and 2019, we have demonstrated that the temporal, geographical, and host-species distribution of GBS ST283 is broader than previously known, whereas the distribution of ST7 and the poikilothermic lineage of GBS are geographically restricted. The gene encoding the human GBS virulence factor C5a peptidase, scpB, was detected in aquatic ST283 from Thailand but not in ST283 from Vietnam or in ST7 from either country, mirroring current reports of GBS strains associated with human sepsis. The observed distribution of strains and virulence genes is likely to reflect a combination of spill-over, host adaptation through the gain and loss of mobile genetic elements, and current biosecurity practices. The plastic nature of the GBS genome and its importance as a human, aquatic, and potentially foodborne pathogen suggests that active surveillance of GBS presence and its evolution in aquaculture systems may be justified. Full article

(This article belongs to the Special Issue Group B-Streptococcus (GBS))

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Open AccessSystematic Review

Impact of Co-Occurrence of Obesity and SARS-CoV-2 Infection during Pregnancy on Placental Pathologies and Adverse Birth Outcomes: A Systematic Review and Narrative Synthesis

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Thaina Ferraz

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Samantha J. Benton

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Israa Zareef

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Oluwatomike Aribaloye

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Enrrico Bloise

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Kristin L. Connor

Pathogens 2023, 12(4), 524; https://doi.org/10.3390/pathogens12040524 - 27 Mar 2023

Abstract

Obesity is a risk factor for severe COVID-19 disease during pregnancy. We hypothesized that the co-occurrence of high maternal body mass index (BMI) and gestational SARS-CoV-2 infection are detrimental to fetoplacental development. We conducted a systematic review following PRISMA/SWiM guidelines and 13 studies [...] Read more.

Obesity is a risk factor for severe COVID-19 disease during pregnancy. We hypothesized that the co-occurrence of high maternal body mass index (BMI) and gestational SARS-CoV-2 infection are detrimental to fetoplacental development. We conducted a systematic review following PRISMA/SWiM guidelines and 13 studies were eligible. In the case series studies (n = 7), the most frequent placental lesions reported in SARS-CoV-2(+) pregnancies with high maternal BMI were chronic inflammation (71.4%, 5/7 studies), fetal vascular malperfusion (FVM) (71.4%, 5/7 studies), maternal vascular malperfusion (MVM) (85.7%, 6/7 studies) and fibrinoids (100%, 7/7 studies). In the cohort studies (n = 4), three studies reported higher rates of chronic inflammation, MVM, FVM and fibrinoids in SARS-CoV-2(+) pregnancies with high maternal BMI (72%, n = 107/149; mean BMI of 30 kg/m²) compared to SARS-CoV-2(−) pregnancies with high BMI (7.4%, n = 10/135). In the fourth cohort study, common lesions observed in placentae from SARS-CoV-2(+) pregnancies with high BMI (n = 187 pregnancies; mean BMI of 30 kg/m²) were chronic inflammation (99%, 186/187), MVM (40%, n = 74/187) and FVM (26%, n = 48/187). BMI and SARS-CoV-2 infection had no effect on birth anthropometry. SARS-CoV-2 infection during pregnancy associates with increased prevalence of placental pathologies, and high BMI in these pregnancies could further affect fetoplacental trajectories. Full article

(This article belongs to the Special Issue Impact of Viruses on Maternal and Fetal Outcome)

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Open AccessArticle

Trimethylamine N-Oxide (TMAO) Mediates Increased Inflammation and Colonization of Bladder Epithelial Cells during a Uropathogenic E. coli Infection In Vitro

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Rongrong Wu

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Ashok Kumar Kumawat

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Isak Demirel

Pathogens 2023, 12(4), 523; https://doi.org/10.3390/pathogens12040523 - 27 Mar 2023

Abstract

Urinary tract infections (UTIs) are among the most common infections in humans and are often caused by uropathogenic E. coli (UPEC). Trimethylamine N-oxide (TMAO) is a proinflammatory metabolite that has been linked to vascular inflammation, atherosclerosis, and chronic kidney disease. As of today, [...] Read more.

Urinary tract infections (UTIs) are among the most common infections in humans and are often caused by uropathogenic E. coli (UPEC). Trimethylamine N-oxide (TMAO) is a proinflammatory metabolite that has been linked to vascular inflammation, atherosclerosis, and chronic kidney disease. As of today, no studies have investigated the effects of TMAO on infectious diseases like UTIs. The aim of this study was to investigate whether TMAO can aggravate bacterial colonization and the release of inflammatory mediators from bladder epithelial cells during a UPEC infection. We found that TMAO aggravated the release of several key cytokines (IL-1β and IL-6) and chemokines (IL-8, CXCL1 and CXCL6) from bladder epithelial cells during a CFT073 infection. We also found that CFT073 and TMAO mediate increased release of IL-8 from bladder epithelial cells via ERK 1/2 signaling and not bacterial growth. Furthermore, we showed that TMAO enhances UPEC colonization of bladder epithelial cells. The data suggest that TMAO may also play a role in infectious diseases. Our results can be the basis of further research to investigate the link between diet, gut microbiota, and urinary tract infection. Full article

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Open AccessOpinion

Pathogenesis of Cerebral Malaria: New Trends and Insights for Developing Adjunctive Therapies

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Praveen Kishore Sahu

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Sanjib Mohanty

Pathogens 2023, 12(4), 522; https://doi.org/10.3390/pathogens12040522 - 27 Mar 2023

Abstract

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, [...] Read more.

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, variations in brain swelling with regard to the age of patients, parasite biomass, and parasite-typing, the essential pathogenetic mechanisms underlying clinical CM have remained elusive. However, a recent series of studies based on molecular, immunologic, and advanced neuroradiologic and machine-learning approaches have unraveled new trends and insights to better understand and focus on the key determinants of CM in humans. This could possibly be the beginning of the design of new and effective adjunctive therapies that may not be common or applicable to the entire malarious world, but that could, rather, be specific to the variations in the determinants of CM. Full article

(This article belongs to the Collection Feature Papers on Parasitic Pathogens)

Open AccessArticle

Risk Factors for Cytomegalovirus Infection and Its Impact on Survival after Living Donor Liver Transplantation in South Korea: A Nested Case-Control Study

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Pathogens 2023, 12(4), 521; https://doi.org/10.3390/pathogens12040521 - 27 Mar 2023

Abstract

Cytomegalovirus (CMV), a common pathogen, causes infectious complications and affects long-term survival after transplantation. Studies examining living donor liver transplantation (LDLT) are limited. This study analyzed the risk factors for CMV infection and its impact on the survival of LDLT patients. A nested [...] Read more.

Cytomegalovirus (CMV), a common pathogen, causes infectious complications and affects long-term survival after transplantation. Studies examining living donor liver transplantation (LDLT) are limited. This study analyzed the risk factors for CMV infection and its impact on the survival of LDLT patients. A nested case–control design retrospectively analyzed data from 952 patients who underwent LDLT from 2005–2021. The incidence of CMV infection for the study cohort was 15.2% at 3 months for LDLT patients managed preemptively. Patients with CMV infections were matched with those without the infection at corresponding time points (index postoperative day) in a 1:2 ratio. Graft survival was significantly lower in the CMV infection group than in the control group. CMV infection was an independent risk factor for graft survival in the matched cohort (HR 1.93, p = 0.012). Independent risk factors for CMV infection were female sex (HR 2.4, p = 0.003), pretransplant MELD (HR 1.06, p = 0.004), pretransplant in-hospital stay (HR 1.83, p = 0.030), ABO incompatibility (HR 2.10, p = 0.009), donor macrovesicular steatosis ≥10% (HR 2.01, p = 0.030), and re-operation before index POD (HR 2.51, p = 0.035). CMV infection is an independent survival risk factor, and its risk factors should be included in the surveillance and treatment of CMV infections after LDLT. Full article

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Open AccessReview

Anti-Inflammatory Benefits of Food Ingredients in Periodontal Diseases

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Evangelos Papathanasiou

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Reem Alreshaid

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Mariely Araujo de Godoi

Pathogens 2023, 12(4), 520; https://doi.org/10.3390/pathogens12040520 - 27 Mar 2023

Abstract

Periodontitis is a multi-faceted inflammatory disease that impacts the gingiva and the structures that support our teeth, and may eventually increase tooth mobility and the risk of tooth loss. Inflammation is a viable therapeutic target of periodontitis for both biologic (dietary) and host [...] Read more.

Periodontitis is a multi-faceted inflammatory disease that impacts the gingiva and the structures that support our teeth, and may eventually increase tooth mobility and the risk of tooth loss. Inflammation is a viable therapeutic target of periodontitis for both biologic (dietary) and host modulatory agents/drugs. Conventional therapeutic approaches for periodontitis, including nonsurgical or surgical periodontal therapy as well as occasional adjunctive antimicrobial therapy, have been only marginally effective. Malnutrition, or at least poor dietary habits, can be highly prevalent among patients with periodontal diseases. As several food nutrients can aid in periodontal healing and regeneration, there is a critical need to evaluate natural dietary sources and supplement ingredients that can counterbalance the inflammatory processes and improve the periodontal status of our patients. Here, we reviewed the current state of knowledge (search period: 2010 to 2022; PubMed and Web of Science) on the anti-inflammatory actions of food ingredients and supplements in clinical studies of patients with periodontal diseases. A diet that includes fruits and vegetables, omega-3 polyunsaturated fatty acids, and supplements of vitamins and plant-derived compounds seems to counteract gingival inflammation and has a promising therapeutic impact in patients with periodontal diseases. Despite the positive indications that several nutrients can be used as an adjunct to periodontal therapy, additional studies with bigger sample sizes and longer follow-up periods are needed to elucidate their therapeutic benefits and the most effective doses and administration. Full article

(This article belongs to the Special Issue Food Ingredients with Antimicrobial and Anti-inflammatory Activity against Infection of Periodontal Pathogens)

Open AccessArticle

Caveats of Using Overexpression Approaches to Screen Cellular Host IFITM Proteins for Antiviral Activity

by

Tina Meischel

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Svenja Fritzlar

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Fernando Villalón-Letelier

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and

Pathogens 2023, 12(4), 519; https://doi.org/10.3390/pathogens12040519 - 27 Mar 2023

Abstract

Ectopic protein overexpression in immortalised cell lines is a commonly used method to screen host factors for their antiviral activity against different viruses. However, the question remains as to what extent such artificial protein overexpression recapitulates endogenous protein function. Previously, we used a [...] Read more.

Ectopic protein overexpression in immortalised cell lines is a commonly used method to screen host factors for their antiviral activity against different viruses. However, the question remains as to what extent such artificial protein overexpression recapitulates endogenous protein function. Previously, we used a doxycycline-inducible overexpression system, in conjunction with approaches to modulate the expression of endogenous protein, to demonstrate the antiviral activity of IFITM1, IFITM2, and IFITM3 against influenza A virus (IAV) but not parainfluenza virus-3 (PIV-3) in A549 cells. We now show that constitutive overexpression of the same IFITM constructs in A549 cells led to a significant restriction of PIV-3 infection by all three IFITM proteins. Variable IFITM mRNA and protein expression levels were detected in A549 cells with constitutive versus inducible overexpression of each IFITM. Our findings show that overexpression approaches can lead to levels of IFITM1, IFITM2, and IFITM3 that significantly exceed those achieved through interferon stimulation of endogenous protein. We propose that exceedingly high levels of overexpressed IFITMs may not accurately reflect the true function of endogenous protein, thus contributing to discrepancies when attributing the antiviral activity of individual IFITM proteins against different viruses. Our findings clearly highlight the caveats associated with overexpression approaches used to screen cellular host proteins for antiviral activity. Full article

(This article belongs to the Special Issue Cell Intrinsic Innate Responses to Viral Infections)

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Open AccessReview

Microbiome and Its Dysbiosis in Inborn Errors of Immunity

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Pathogens 2023, 12(4), 518; https://doi.org/10.3390/pathogens12040518 - 27 Mar 2023

Abstract

Inborn errors of immunity (IEI) can present with infections, autoimmunity, lymphoproliferation, granulomas, and malignancy. IEIs are due to genetic abnormalities that disrupt normal host-immune response or immune regulation. The microbiome appears essential for maintaining host immunity, especially in patients with a defective immune [...] Read more.

Inborn errors of immunity (IEI) can present with infections, autoimmunity, lymphoproliferation, granulomas, and malignancy. IEIs are due to genetic abnormalities that disrupt normal host-immune response or immune regulation. The microbiome appears essential for maintaining host immunity, especially in patients with a defective immune system. Altered gut microbiota in patients with IEI can lead to clinical symptoms. Microbial dysbiosis is the consequence of an increase in pro-inflammatory bacteria or a reduction in anti-inflammatory bacteria. However, functional and compositional differences in microbiota are also involved. Dysbiosis and a reduced alpha-diversity are well documented, particularly in conditions like common variable immunodeficiency. Deranged microbiota is also seen in Wiskott–Aldrich syndrome, severe combined immunodeficiency, chronic granulomatous disease, selective immunoglobulin-A deficiency, Hyper IgE syndrome (HIGES), X-linked lymphoproliferative disease-2, immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome, and defects of IL10 signalling. Distinct gastrointestinal, respiratory, and cutaneous symptoms linked to dysbiosis are seen in several IEIs, emphasizing the importance of microbiome identification. In this study, we discuss the processes that maintain immunological homeostasis between commensals and the host and the disruptions thereof in patients with IEIs. As the connection between microbiota, host immunity, and infectious illnesses is better understood, microbiota manipulation as a treatment strategy or infection prevention method would be more readily employed. Therefore, optimal prebiotics, probiotics, postbiotics, and fecal microbial transplantation can be promising strategies to restore the microbiota and decrease disease pathology in patients with IEIs. Full article

(This article belongs to the Special Issue Infection in Inborn Errors of Immunity)

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