Pathogens

23 pages, 3703 KiB

Open AccessEditor’s ChoiceArticle

Simulation of Foot-and-Mouth Disease Spread and Effects of Mitigation Strategies to Support Veterinary Contingency Planning in Denmark

by Beate Conrady, Sten Mortensen, Søren Saxmose Nielsen, Hans Houe, Francisco Fernando Calvo-Artavia, Johanne Ellis-Iversen and Anette Boklund

Pathogens 2023, 12(3), 435; https://doi.org/10.3390/pathogens12030435 - 09 Mar 2023

Cited by 2 | Viewed by 2010

Abstract

To forge a path towards livestock disease emergency preparedness in Denmark, 15 different strategies to mitigate foot-and-mouth disease (FMD) were examined by modelling epidemics initiated in cattle, pig or small ruminant herds across various production systems located in four different Danish regions (Scenario [...] Read more.

To forge a path towards livestock disease emergency preparedness in Denmark, 15 different strategies to mitigate foot-and-mouth disease (FMD) were examined by modelling epidemics initiated in cattle, pig or small ruminant herds across various production systems located in four different Danish regions (Scenario 1), or in one specific livestock production system within each of the three species geographically distributed throughout Denmark (Scenario 2). When additional mitigation strategies were implemented on top of basic control strategies in the European foot-and-mouth disease spread model (EuFMDiS), no significant benefits were predicted in terms of the number of infected farms, the epidemic control duration, and the total economic cost. Further, the model results indicated that the choice of index herd, the resources for outbreak control, and the detection time of FMD significantly influenced the course of an epidemic. The present study results emphasise the importance of basic mitigation strategies, including an effective back-and-forward traceability system, adequate resources for outbreak response, and a high level of awareness among farmers and veterinarians concerning the detection and reporting of FMD at an early stage of an outbreak for FMD control in Denmark. Full article

(This article belongs to the Special Issue Monitoring, Prevention and Control of Infectious Animal Diseases)

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20 pages, 5734 KiB

Open AccessEditor’s ChoiceReview

Occurrence, Distribution, and Management of Aphid-Transmitted Viruses in Cucurbits in Spain

by Celia De Moya-Ruiz, Pedro Gómez and Miguel Juárez

Pathogens 2023, 12(3), 422; https://doi.org/10.3390/pathogens12030422 - 07 Mar 2023

Cited by 4 | Viewed by 2946

Abstract

The effectiveness of pest and disease management in crops relies on knowledge about their presence and distribution in crop-producing areas. Aphids and whiteflies are among the main threats to vegetable crops since these hemipterans feed on plants, causing severe damage, and are also [...] Read more.

The effectiveness of pest and disease management in crops relies on knowledge about their presence and distribution in crop-producing areas. Aphids and whiteflies are among the main threats to vegetable crops since these hemipterans feed on plants, causing severe damage, and are also able to transmit a large number of devastating plant viral diseases. In particular, the widespread occurrence of aphid-transmitted viruses in cucurbit crops, along with the lack of effective control measures, makes surveillance programs and virus epidemiology necessary for providing sound advice and further integration into the management strategies that can ensure sustainable food production. This review describes the current presence and distribution of aphid-transmitted viruses in cucurbits in Spain, providing valuable epidemiological information, including symptom expressions of virus-infected plants for further surveillance and viral detection. We also provide an overview of the current measures for virus infection prevention and control strategies in cucurbits and indicate the need for further research and innovative strategies against aphid pests and their associated viral diseases. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)

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12 pages, 684 KiB

Open AccessEditor’s ChoiceReview

Preventing Persistence of HPV Infection with Natural Molecules

by Antonio Simone Laganà, Vito Chiantera, Sandro Gerli, Sara Proietti, Elisa Lepore, Vittorio Unfer, Jose Carugno and Alessandro Favilli

Pathogens 2023, 12(3), 416; https://doi.org/10.3390/pathogens12030416 - 06 Mar 2023

Cited by 3 | Viewed by 7091

Abstract

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination [...] Read more.

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence. Full article

(This article belongs to the Special Issue Epidemiology of Human Papillomavirus Infection)

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13 pages, 792 KiB

Open AccessEditor’s ChoiceReview

Effective Treatments of UTI—Is Intravesical Therapy the Future?

by Chris J. Morris, Jennifer L. Rohn, Scott Glickman and Kylie J. Mansfield

Pathogens 2023, 12(3), 417; https://doi.org/10.3390/pathogens12030417 - 06 Mar 2023

Cited by 2 | Viewed by 2322

Abstract

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is [...] Read more.

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)

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18 pages, 1547 KiB

Open AccessEditor’s ChoiceArticle

Bacterial and Viral Pathogens with One Health Relevance in Invasive Raccoons (Procyon lotor, Linné 1758) in Southwest Germany

by Nico P. Reinhardt, Judith Köster, Astrid Thomas, Janosch Arnold, Robert Fux and Reinhard K. Straubinger

Pathogens 2023, 12(3), 389; https://doi.org/10.3390/pathogens12030389 - 01 Mar 2023

Cited by 4 | Viewed by 2224

Abstract

In Europe, raccoons are invasive neozoons with their largest population in Germany. Globally, this mesocarnivore acts as a wildlife reservoir for many (non-)zoonotic (re-)emerging pathogens, but very little epidemiological data is available for southwest Germany. This exploratory study aimed to screen free-ranging raccoons [...] Read more.

In Europe, raccoons are invasive neozoons with their largest population in Germany. Globally, this mesocarnivore acts as a wildlife reservoir for many (non-)zoonotic (re-)emerging pathogens, but very little epidemiological data is available for southwest Germany. This exploratory study aimed to screen free-ranging raccoons in Baden-Wuerttemberg (BW, Germany) for the occurrence of selected pathogens with One Health relevance. Organ tissue and blood samples collected from 102 animals, obtained by hunters in 2019 and 2020, were subsequently analysed for two bacterial and four viral pathogens using a qPCR approach. Single samples were positive for the carnivore protoparvovirus-1 (7.8%, n = 8), canine distemper virus (6.9%, n = 7), pathogenic Leptospira spp. (3.9%, n = 4) and Anaplasma phagocytophilum (15.7%, n = 16). West Nile virus and influenza A virus were not detected. Due to their invasive behaviour and synanthropic habit, raccoons may increase the risk of infections for wildlife, domestic animals, zoo animals and humans by acting as a link between them. Therefore, further studies should be initiated to evaluate these risks. Full article

(This article belongs to the Special Issue Surveillance of Zoonotic Pathogens Carried by Wildlife)

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15 pages, 5718 KiB

Open AccessEditor’s ChoiceArticle

Design and Optimization of a Monkeypox virus Specific Serological Assay

by Taha Y. Taha, Michael B. Townsend, Jan Pohl, Kevin L. Karem, Inger K. Damon, Placide Mbala Kingebeni, Jean-Jacques Muyembe Tamfum, James W. Martin, Phillip R. Pittman, John W. Huggins, Panayampalli S. Satheshkumar, Dennis A. Bagarozzi, Jr., Mary G. Reynolds and Laura J. Hughes

Pathogens 2023, 12(3), 396; https://doi.org/10.3390/pathogens12030396 - 01 Mar 2023

Cited by 6 | Viewed by 2267

Abstract

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the [...] Read more.

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak. Full article

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13 pages, 1195 KiB

Open AccessEditor’s ChoiceArticle

Screening for Influenza and Morbillivirus in Seals and Porpoises in the Baltic and North Sea

by Iben Stokholm, Christine Baechlein, Sara Persson, Anna Roos, Anders Galatius, Line Anker Kyhn, Signe Sveegaard, Charlotte Bie Thøstesen, Morten Tange Olsen, Paul Becher and Ursula Siebert

Pathogens 2023, 12(3), 357; https://doi.org/10.3390/pathogens12030357 - 21 Feb 2023

Cited by 2 | Viewed by 2235

Abstract

Historically, the seals and harbour porpoises of the Baltic Sea and North Sea have been subjected to hunting, chemical pollutants and repeated mass mortalities, leading to significant population fluctuations. Despite the conservation implications and the zoonotic potential associated with viral disease outbreaks in [...] Read more.

Historically, the seals and harbour porpoises of the Baltic Sea and North Sea have been subjected to hunting, chemical pollutants and repeated mass mortalities, leading to significant population fluctuations. Despite the conservation implications and the zoonotic potential associated with viral disease outbreaks in wildlife, limited information is available on the circulation of viral pathogens in Baltic Sea seals and harbour porpoises. Here, we investigated the presence of the influenza A virus (IAV), the phocine distemper virus (PDV) and the cetacean morbillivirus (CeMV) in tracheal swabs and lung tissue samples from 99 harbour seals, 126 grey seals, 73 ringed seals and 78 harbour porpoises collected in the Baltic Sea and North Sea between 2002–2019. Despite screening 376 marine mammals collected over nearly two decades, we only detected one case of PDV and two cases of IAV linked to the documented viral outbreaks in seals in 2002 and 2014, respectively. Although we find no evidence of PDV and IAV during intermediate years, reports of isolated cases of PDV in North Sea harbour seals and IAV (H5N8) in Baltic and North Sea grey seals suggest introductions of those pathogens within the sampling period. Thus, to aid future monitoring efforts we highlight the need for a standardized and continuous sample collection of swabs, tissue and blood samples across Baltic Sea countries. Full article

(This article belongs to the Special Issue Wildlife Hosts Pathogen Interaction)

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29 pages, 2488 KiB

Open AccessEditor’s ChoiceReview

Orthopoxvirus Zoonoses—Do We Still Remember and Are Ready to Fight?

by Małgorzata Gieryńska, Lidia Szulc-Dąbrowska, Justyna Struzik, Karolina Paulina Gregorczyk-Zboroch, Matylda Barbara Mielcarska, Felix Ngosa Toka, Ada Schollenberger and Zuzanna Biernacka

Pathogens 2023, 12(3), 363; https://doi.org/10.3390/pathogens12030363 - 21 Feb 2023

Cited by 5 | Viewed by 2108

Abstract

The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines [...] Read more.

The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines induced strong, humoral, and cell-mediated immune responses, protecting for decades after immunization, not only against smallpox but also against other zoonotic orthopoxviruses that now represent a significant threat to public health. Here we review the major aspects regarding orthopoxviruses’ zoonotic infections, factors responsible for viral transmissions, as well as the emerging problem of the increased number of monkeypox cases recently reported. The development of prophylactic measures against poxvirus infections, especially the current threat caused by the monkeypox virus, requires a profound understanding of poxvirus immunobiology. The utilization of animal and cell line models has provided good insight into host antiviral defenses as well as orthopoxvirus evasion mechanisms. To survive within a host, orthopoxviruses encode a large number of proteins that subvert inflammatory and immune pathways. The circumvention of viral evasion strategies and the enhancement of major host defenses are key in designing novel, safer vaccines, and should become the targets of antiviral therapies in treating poxvirus infections. Full article

(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)

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17 pages, 2454 KiB

Open AccessEditor’s ChoiceArticle

Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors

by Marion Schuller, Tryfon Zarganes-Tzitzikas, James Bennett, Stephane De Cesco, Daren Fearon, Frank von Delft, Oleg Fedorov, Paul E. Brennan and Ivan Ahel

Pathogens 2023, 12(2), 324; https://doi.org/10.3390/pathogens12020324 - 15 Feb 2023

Cited by 3 | Viewed by 2788

Abstract

The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire [...] Read more.

The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire that was identified as a potential target for the development of antiviral agents, due to its critical role in viral replication and consequent pathogenicity in the host. By combining virtual and biophysical screening efforts, we discovered several experimental small molecules and FDA-approved drugs as inhibitors of the NSP3 macrodomain. Analogue characterisation of the hit matter and crystallographic studies confirming binding modes, including that of the antibiotic compound aztreonam, to the active site of the macrodomain provide valuable structure–activity relationship information that support current approaches and open up new avenues for NSP3 macrodomain inhibitor development. Full article

(This article belongs to the Special Issue ADP-Ribosylation in Pathogens)

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12 pages, 1364 KiB

Open AccessEditor’s ChoiceReview

The Evolution of the Safety of Plasma Products from Pathogen Transmission—A Continuing Narrative

by Albert Farrugia

Pathogens 2023, 12(2), 318; https://doi.org/10.3390/pathogens12020318 - 15 Feb 2023

Cited by 5 | Viewed by 2918

Abstract

Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is [...] Read more.

Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is an essential part of the large-scale manufacture of these products and is required for good manufacturing practice (GMP). Early observations of the transmission of hepatitis by pooled plasma and serum led to the incorporation of heat treatment of the albumin solution produced by industrial Cohn fractionation of plasma. This led to an absence of pathogen transmission by albumin over decades, during which hepatitis continued to be transmitted by other early plasma fractions, as well as through mainstream blood transfusions. This risk was decreased greatly over the 1960s as an understanding of the epidemiology and viral aetiology of transfusion-transmitted hepatitis led to the exclusion of high-risk groups from the donor population and the development of a blood screening test for hepatitis B. Despite these measures, the first plasma concentrates to treat haemophilia transmitted hepatitis B and other, poorly understood, forms of parenterally transmitted hepatitis. These risks were considered to be acceptable given the life-saving nature of the haemophilia treatment products. The emergence of the human immunodeficiency virus (HIV) as a transfusion-transmitted infection in the early 1980s shifted the focus of attention to this virus, which proved to be vulnerable to a number of inactivation methods introduced during manufacture. Further developments in the field obviated the risk of hepatitis C virus (HCV) which had also infected chronic recipients of plasma products, including haemophilia patients and immunodeficient patients receiving immunoglobulin. The convergence of appropriate donor selection driven by knowledge of viral epidemiology, the development of blood screening now based on molecular diagnostics, and the incorporation of viral inactivation techniques in the manufacturing process are now recognised as constituting a “safety tripod” of measures contributing to safety from pathogen transmission. Of these three components, viral inactivation during manufacture is the major contributor and has proven to be the bulwark securing the safety of plasma derivatives over the past thirty years. Concurrently, the safety of banked blood and components continues to depend on donor selection and screening, in the absence of universally adopted pathogen reduction technology. This has resulted in an inversion in the relative safety of the products of blood banking compared to plasma products. Overall, the experience gained in the past decades has resulted in an absence of pathogen transmission from the current generation of plasma derivatives, but maintaining vigilance, and the surveillance of the emergence of infectious agents, is vital to ensure the continued efficacy of the measures in place and the development of further interventions aimed at obviating safety threats. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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16 pages, 1115 KiB

Open AccessEditor’s ChoiceReview

HPV and Cervical Cancer: A Review of Epidemiology and Screening Uptake in the UK

by Sunyoung Choi, Ayden Ismail, George Pappas-Gogos and Stergios Boussios

Pathogens 2023, 12(2), 298; https://doi.org/10.3390/pathogens12020298 - 11 Feb 2023

Cited by 21 | Viewed by 8624

Abstract

Cervical cancer is the fourth most common malignancy in females worldwide, and a leading cause of death in the United Kingdom (UK). The human papillomavirus (HPV) is the strongest risk factor for developing cervical intraepithelial neoplasia and cancer. Across the UK, the national [...] Read more.

Cervical cancer is the fourth most common malignancy in females worldwide, and a leading cause of death in the United Kingdom (UK). The human papillomavirus (HPV) is the strongest risk factor for developing cervical intraepithelial neoplasia and cancer. Across the UK, the national HPV immunisation programme, introduced in 2008, has been successful in protecting against HPV-related infections. Furthermore, the National Health Service (NHS) implemented the cytology-based cervical cancer screening service to all females aged 25 to 64, which has observed a decline in cervical cancer incidence. In the UK, there has been an overall decline in age-appropriate coverage since April 2010. In 2019, the COVID-19 pandemic disrupted NHS cancer screening and immunisation programmes, leading to a 6.8% decreased uptake of cervical cancer screening from the previous year. Engagement with screening has also been associated with social deprivation. In England, incidence rates of cervical cancer were reported to be 65% higher in the most deprived areas compared to the least, with lifestyle factors such as cigarette consumption contributing to 21% of cervical cancer cases. In this article, we provide an update on the epidemiology of cervical cancer, and HPV pathogenesis and transmission, along with the current prevention programmes within the NHS. Full article

(This article belongs to the Special Issue Oncopathogens)

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17 pages, 587 KiB

Open AccessEditor’s ChoiceReview

Advances in Babesia Vaccine Development: An Overview

by Michał Jerzak, Albert Gandurski, Marta Tokaj, Weronika Stachera, Magdalena Szuba and Monika Dybicz

Pathogens 2023, 12(2), 300; https://doi.org/10.3390/pathogens12020300 - 11 Feb 2023

Cited by 7 | Viewed by 3850

Abstract

Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular Babesia parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. [...] Read more.

Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular Babesia parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. Since the current preventive measures against babesiosis are insufficient, there is increasing pressure to develop a vaccine. In this review, we survey the achievements and recent advances in the creation of antibabesiosis vaccine. The scope of this review includes the development of a vaccine against B. microti, B. bovis, B. bigemina, B. orientalis and B. divergens. Here, we present different strategies in their progress and evaluation. Scientists worldwide are still trying to find new targets for a vaccine that would not only reduce symptoms among animals but also prevent the further spread of the disease. Molecular candidates for the production of a vaccine against various Babesia spp. are presented. Our study also describes the current prospects of vaccine evolution for successful Babesia parasites elimination. Full article

(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)

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11 pages, 1369 KiB

Open AccessEditor’s ChoiceArticle

Phytophthora Species Involved in Alnus glutinosa Decline in Portugal

by Carlo Bregant, Eduardo Batista, Sandra Hilário, Benedetto T. Linaldeddu and Artur Alves

Pathogens 2023, 12(2), 276; https://doi.org/10.3390/pathogens12020276 - 08 Feb 2023

Cited by 8 | Viewed by 2045

Abstract

Recent field surveys conducted in five common alder ecosystems in Portugal have shown the occurrence of severe canopy dieback, bleeding canker and root rot symptoms indicative of Phytophthora infections. Isolations from symptomatic tissues, rhizosphere and water samples yielded a total of 13 Phytophthora [...] Read more.

Recent field surveys conducted in five common alder ecosystems in Portugal have shown the occurrence of severe canopy dieback, bleeding canker and root rot symptoms indicative of Phytophthora infections. Isolations from symptomatic tissues, rhizosphere and water samples yielded a total of 13 Phytophthora species belonging to 6 phylogenetic clades, including P. lacustris (13 isolates), P. multivora (10), P. amnicola (9), P. chlamydospora (6), P. polonica (6), P. bilorbang (4), P. plurivora (4), P. cinnamomi (3), P. asparagi (2), P. cactorum (2), P. pseudocryptogea (2), P. gonapodyides (1) and P. rosacearum (1). Results of the pathogenicity test confirmed the complex aetiology of common alder decline and the additional risk posed by Phytophthora multivora to the riparian habitats in Portugal. At the same time, the diversity of Phytophthora assemblages detected among the investigated sites suggests that different species could contribute to causing the same symptoms on this host. Two species, P. amnicola and P. rosacearum, are reported here for the first time in natural ecosystems in Europe. Full article

(This article belongs to the Special Issue Advances and Challenges in Understanding and Management of Diseases Caused by Oomycetes)

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15 pages, 866 KiB

Open AccessEditor’s ChoiceReview

A Review on the Immunological Response against Trypanosoma cruzi

by Giusi Macaluso, Francesca Grippi, Santina Di Bella, Valeria Blanda, Francesca Gucciardi, Alessandra Torina, Annalisa Guercio and Vincenza Cannella

Pathogens 2023, 12(2), 282; https://doi.org/10.3390/pathogens12020282 - 08 Feb 2023

Cited by 11 | Viewed by 2932

Abstract

Chagas disease is a chronic systemic infection transmitted by Trypanosoma cruzi. Its life cycle consists of different stages in vector insects and host mammals. Trypanosoma cruzi strains cause different clinical manifestations of Chagas disease alongside geographic differences in morbidity and mortality. Natural killer [...] Read more.

Chagas disease is a chronic systemic infection transmitted by Trypanosoma cruzi. Its life cycle consists of different stages in vector insects and host mammals. Trypanosoma cruzi strains cause different clinical manifestations of Chagas disease alongside geographic differences in morbidity and mortality. Natural killer cells provide the cytokine interferon-gamma in the initial phases of T. cruzi infection. Phagocytes secrete cytokines that promote inflammation and activation of other cells involved in defence. Dendritic cells, monocytes and macrophages modulate the adaptive immune response, and B lymphocytes activate an effective humoral immune response to T. cruzi. This review focuses on the main immune mechanisms acting during T. cruzi infection, on the strategies activated by the pathogen against the host cells, on the processes involved in inflammasome and virulence factors and on the new strategies for preventing, controlling and treating this disease. Full article

(This article belongs to the Special Issue Current Research on Trypanosoma cruzi Infection)

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21 pages, 729 KiB

Open AccessEditor’s ChoiceReview

Borrelia miyamotoi: A Comprehensive Review

by Dawn W. Cleveland, Cassidy C. Anderson and Catherine A. Brissette

Pathogens 2023, 12(2), 267; https://doi.org/10.3390/pathogens12020267 - 07 Feb 2023

Cited by 10 | Viewed by 3469

Abstract

Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern Hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). Borrelia miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and [...] Read more.

Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern Hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). Borrelia miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus, has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein, we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi. Full article

(This article belongs to the Special Issue Pathogenesis, Epidemiology, Host Response and Control of Lyme Disease and Other Tick-Borne Diseases)

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16 pages, 3502 KiB

Open AccessEditor’s ChoiceReview

A Review of Major Patents on Potential Malaria Vaccine Targets

by Reysla Maria da Silveira Mariano, Ana Alice Maia Gonçalves, Diana Souza de Oliveira, Helen Silva Ribeiro, Diogo Fonseca Soares Pereira, Ingrid Soares Santos, Daniel Ferreira Lair, Augusto Ventura da Silva, Alexsandro Sobreira Galdino, Miguel Angel Chávez-Fumagalli, Denise da Silveira-Lemos, Walderez Ornelas Dutra and Rodolfo Cordeiro Giunchetti

Pathogens 2023, 12(2), 247; https://doi.org/10.3390/pathogens12020247 - 03 Feb 2023

Cited by 2 | Viewed by 2998

Abstract

Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the [...] Read more.

Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite’s complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite’s replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle. Full article

(This article belongs to the Special Issue Neglected and Emergent Diseases)

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25 pages, 7078 KiB

Open AccessEditor’s ChoiceReview

Epidemiology of Ebolaviruses from an Etiological Perspective

by Sahil Jain, Svetlana Khaiboullina, Ekaterina Martynova, Sergey Morzunov and Manoj Baranwal

Pathogens 2023, 12(2), 248; https://doi.org/10.3390/pathogens12020248 - 03 Feb 2023

Cited by 5 | Viewed by 4774

Abstract

Since the inception of the ebolavirus in 1976, 32 outbreaks have resulted in nearly 15,350 deaths in more than ten countries of the African continent. In the last decade, the largest (2013–2016) and second largest (2018–2020) ebolavirus outbreaks have occurred in West Africa [...] Read more.

Since the inception of the ebolavirus in 1976, 32 outbreaks have resulted in nearly 15,350 deaths in more than ten countries of the African continent. In the last decade, the largest (2013–2016) and second largest (2018–2020) ebolavirus outbreaks have occurred in West Africa (mainly Guinea, Liberia, and Sierra Leone) and the Democratic Republic of the Congo, respectively. The 2013–2016 outbreak indicated an alarming geographical spread of the virus and was the first to qualify as an epidemic. Hence, it is imperative to halt ebolavirus progression and develop effective countermeasures. Despite several research efforts, ebolaviruses’ natural hosts and secondary reservoirs still elude the scientific world. The primary source responsible for infecting the index case is also unknown for most outbreaks. In this review, we summarize the history of ebolavirus outbreaks with a focus on etiology, natural hosts, zoonotic reservoirs, and transmission mechanisms. We also discuss the reasons why the African continent is the most affected region and identify steps to contain this virus. Full article

(This article belongs to the Special Issue Surveillance of Zoonotic Pathogens Carried by Wildlife)

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27 pages, 3767 KiB

Open AccessEditor’s ChoiceReview

SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants

by David B. Reeg, Maike Hofmann, Christoph Neumann-Haefelin, Robert Thimme and Hendrik Luxenburger

Pathogens 2023, 12(2), 244; https://doi.org/10.3390/pathogens12020244 - 03 Feb 2023

Cited by 7 | Viewed by 3146

Abstract

Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T [...] Read more.

Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T cells being linked to efficient viral clearance. Vaccination against SARS-CoV-2 induces both CD4+ and CD8+ T cell responses and permits protection from severe COVID-19, including infection with the currently circulating variants of concern. Nevertheless, in immunocompromised individuals, first data imply significantly impaired SARS-CoV-2-specific immune responses after both natural infection and vaccination. Hence, these high-risk groups require particular consideration, not only in routine clinical practice, but also in the development of future vaccination strategies. In order to assist physicians in the guidance of immunocompromised patients, concerning the management of infection or the benefit of (booster) vaccinations, this review aims to provide a concise overview of the current knowledge about SARS-CoV-2-specific cellular immune responses in the vulnerable cohorts of cancer patients, people living with HIV (PLWH), and solid organ transplant recipients (SOT). Recent findings regarding the virus-specific cellular immunity in these differently immunocompromised populations might influence clinical decision-making in the future. Full article

(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)

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16 pages, 685 KiB

Open AccessEditor’s ChoiceReview

Factors Affecting Arbovirus Midgut Escape in Mosquitoes

by Alexis Carpenter and Rollie J. Clem

Pathogens 2023, 12(2), 220; https://doi.org/10.3390/pathogens12020220 - 31 Jan 2023

Cited by 6 | Viewed by 4630

Abstract

Arboviral diseases spread by mosquitoes cause significant morbidity and mortality throughout much of the world. The treatment and prevention of these diseases through medication and vaccination is often limited, which makes controlling arboviruses at the level of the vector ideal. One way to [...] Read more.

Arboviral diseases spread by mosquitoes cause significant morbidity and mortality throughout much of the world. The treatment and prevention of these diseases through medication and vaccination is often limited, which makes controlling arboviruses at the level of the vector ideal. One way to prevent the spread of an arbovirus would be to stop its vector from developing a disseminated infection, which is required for the virus to make its way to the saliva of the mosquito to be potentially transmitted to a new host. The midgut of the mosquito provides one such opportunity to stop an arbovirus in its tracks. It has been known for many years that in certain arbovirus–vector combinations, or under certain circumstances, an arbovirus can infect and replicate in the midgut but is unable to escape from the tissue to cause disseminated infection. This situation is known as a midgut escape barrier. If we better understand why this barrier occurs, it might aid in the development of more informed control strategies. In this review, we discuss how the midgut escape barrier contributes to virus–vector specificity and possible mechanisms that may allow this barrier to be overcome in successful virus–vector combinations. We also discuss several of the known factors that either increase or decrease the likelihood of midgut escape. Full article

(This article belongs to the Special Issue Advances in Mosquito-Borne Pathogens and Diseases)

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20 pages, 543 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Evaluation of Genomic Typing Methods in the Salmonella Reference Laboratory in Public Health, England, 2012–2020

by Marie Anne Chattaway, Anaïs Painset, Gauri Godbole, Saheer Gharbia and Claire Jenkins

Pathogens 2023, 12(2), 223; https://doi.org/10.3390/pathogens12020223 - 31 Jan 2023

Cited by 5 | Viewed by 3334

Abstract

We aim to provide an evidence-based evaluation of whole genome sequence (WGS) methods, employed at the Salmonella reference laboratory in England, in terms of its impact on public health and whether these methods remain a fit for purpose test under UKAS ISO 15189. [...] Read more.

We aim to provide an evidence-based evaluation of whole genome sequence (WGS) methods, employed at the Salmonella reference laboratory in England, in terms of its impact on public health and whether these methods remain a fit for purpose test under UKAS ISO 15189. The evaluation of the genomic methods were mapped against the value of detecting microbiological clusters to support the investigation of food-borne outbreaks of Salmonella in England between 2012–2020. The analysis of WGS with both SNP- and allelic-based methods provided an unprecedented level of strain discrimination and detection of additional clusters when comparing to all of the previous typing methods. The robustness of the routine genomic sequencing at the reference laboratory ensured confidence in the microbiological identifications, even in large outbreaks with complex international food distribution networks. There was evidence that the phylogeny derived from the WGS data can be used to inform the provenance of strains and support discrimination between domestic and non-domestic transmission events. Further insight on the evolutionary context of the emerging pathogenic strains was enabled with a deep dive of the phylogenetic data, including the detection of nested clusters. The public availability of the WGS data linked to the clinical, epidemiological and environmental context of the sequenced strains has improved the trace-back investigations during outbreaks. The global expansion in the use of WGS-based typing in reference laboratories has shown that the WGS methods are a fit for purpose test in public health as it has ensured the rapid implementation of interventions to protect public health, informed risk assessment and has facilitated the management of national and international food-borne outbreaks of Salmonella. Full article

(This article belongs to the Special Issue Genomic Epidemiology of Foodborne Pathogens 2.0)

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19 pages, 1628 KiB

Open AccessEditor’s ChoiceArticle

Seroprevalence of Tick-Borne Encephalitis (TBE) Virus Antibodies in Wild Rodents from Two Natural TBE Foci in Bavaria, Germany

by Philipp Johannes Brandenburg, Anna Obiegala, Hannah Maureen Schmuck, Gerhard Dobler, Lidia Chitimia-Dobler and Martin Pfeffer

Pathogens 2023, 12(2), 185; https://doi.org/10.3390/pathogens12020185 - 25 Jan 2023

Cited by 6 | Viewed by 1720

Abstract

Tick-borne encephalitis (TBE) is Eurasia’s most important tick-borne viral disease. Rodents play an important role as natural hosts. Longitudinal studies on the dynamics of the seroprevalence rates in wild rodents in natural foci over the year are rare, and the dynamics of the [...] Read more.

Tick-borne encephalitis (TBE) is Eurasia’s most important tick-borne viral disease. Rodents play an important role as natural hosts. Longitudinal studies on the dynamics of the seroprevalence rates in wild rodents in natural foci over the year are rare, and the dynamics of the transmission cycle still need to be understood. To better understand the infection dynamics, rodents were captured in a capture-mark-release-recapture-study in two natural foci in Bavaria, Germany, monthly from March 2019 to October 2022. Overall, 651 blood and thoracic lavage samples from 478 different wild rodents (Clethrionomys glareolus and Apodemus flavicollis) were analyzed for antibodies against tick-borne encephalitis virus (TBEV) by indirect immunofluorescence assay (IIFA) and confirmed using a serum neutralization test (SNT). Furthermore, a generalized linear mixed model (GLMM) analysis was performed to investigate ecological and individual factors for the probability of infection in rodents. Clethrionomys glareolus (19.4%) had a higher seroprevalence than A. flavicollis (10.5%). Within Cl. glareolus, more males (40.4%) than females (15.6%) were affected, and more adults (25.4%) than juveniles (9.8%). The probability of infection of rodents rather depends on factors such as species, sex, and age than on the study site of a natural focus, year, and season. The high incidence rates of rodents, particularly male adult bank voles, highlight their critical role in the transmission cycle of TBEV in a natural focus and demonstrate that serologically positive rodents can be reliably detected in a natural focus regardless of season or year. In addition, these data contribute to a better understanding of the TBEV cycle and thus could improve preventive strategies for human infections. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis Virus)

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32 pages, 1237 KiB

Open AccessEditor’s ChoiceReview

Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines—A Review

by Wojciech Zygner, Olga Gójska-Zygner and Luke J. Norbury

Pathogens 2023, 12(2), 166; https://doi.org/10.3390/pathogens12020166 - 20 Jan 2023

Cited by 7 | Viewed by 6099

Abstract

Canine babesiosis is a tick-borne protozoan disease caused by intraerythrocytic parasites of the genus Babesia. The infection may lead to anemia in infected dogs. However, anemia is not directly caused by the pathogen. The parasite’s developmental stages only have a marginal role [...] Read more.

Canine babesiosis is a tick-borne protozoan disease caused by intraerythrocytic parasites of the genus Babesia. The infection may lead to anemia in infected dogs. However, anemia is not directly caused by the pathogen. The parasite’s developmental stages only have a marginal role in contributing to a decreased red blood cell (RBC) count. The main cause of anemia in affected dogs is the immune response to the infection. This response includes antibody production, erythrophagocytosis, oxidative damage of RBCs, complement activation, and antibody-dependent cellular cytotoxicity. Moreover, both infected and uninfected erythrocytes are retained in the spleen and sequestered in micro-vessels. All these actions are driven by pro-inflammatory cytokines and chemokines, especially IFN-γ, TNF-α, IL-6, and IL-8. Additionally, imbalance between the actions of pro- and anti-inflammatory cytokines plays a role in patho-mechanisms leading to anemia in canine babesiosis. This article is a review of the studies on the pathogenesis of anemia in canine babesiosis and related diseases, such as bovine or murine babesiosis and human or murine malaria, and the role of pro-inflammatory cytokines and chemokines in the mechanisms leading to anemia in infected dogs. Full article

(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)

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11 pages, 3758 KiB

Open AccessEditor’s ChoiceArticle

Zoonotic Mutation of Highly Pathogenic Avian Influenza H5N1 Virus Identified in the Brain of Multiple Wild Carnivore Species

by Sandra Vreman, Marja Kik, Evelien Germeraad, Rene Heutink, Frank Harders, Marcel Spierenburg, Marc Engelsma, Jolianne Rijks, Judith van den Brand and Nancy Beerens

Pathogens 2023, 12(2), 168; https://doi.org/10.3390/pathogens12020168 - 20 Jan 2023

Cited by 20 | Viewed by 27696

Abstract

Wild carnivore species infected with highly pathogenic avian influenza (HPAI) virus subtype H5N1 during the 2021–2022 outbreak in the Netherlands included red fox (Vulpes vulpes), polecat (Mustela putorius), otter (Lutra lutra), and badger (Meles meles). [...] Read more.

Wild carnivore species infected with highly pathogenic avian influenza (HPAI) virus subtype H5N1 during the 2021–2022 outbreak in the Netherlands included red fox (Vulpes vulpes), polecat (Mustela putorius), otter (Lutra lutra), and badger (Meles meles). Most of the animals were submitted for testing because they showed neurological signs. In this study, the HPAI H5N1 virus was detected by PCR and/or immunohistochemistry in 11 animals and was primarily present in brain tissue, often associated with a (meningo) encephalitis in the cerebrum. In contrast, the virus was rarely detected in the respiratory tract and intestinal tract and associated lesions were minimal. Full genome sequencing followed by phylogenetic analysis demonstrated that these carnivore viruses were related to viruses detected in wild birds in the Netherlands. The carnivore viruses themselves were not closely related, and the infected carnivores did not cluster geographically, suggesting that they were infected separately. The mutation PB2-E627K was identified in most carnivore virus genomes, providing evidence for mammalian adaptation. This study showed that brain samples should be included in wild life surveillance programs for the reliable detection of the HPAI H5N1 virus in mammals. Surveillance of the wild carnivore population and notification to the Veterinary Authority are important from a one-heath perspective, and instrumental to pandemic preparedness. Full article

(This article belongs to the Collection Emerging and Re-emerging Pathogens)

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25 pages, 1993 KiB

Open AccessEditor’s ChoiceReview

Endogenous Retroviruses as Modulators of Innate Immunity

by Eric Russ and Sergey Iordanskiy

Pathogens 2023, 12(2), 162; https://doi.org/10.3390/pathogens12020162 - 19 Jan 2023

Cited by 13 | Viewed by 4969

Abstract

Endogenous retroviruses (ERVs), or LTR retrotransposons, are a class of transposable elements that are highly represented in mammalian genomes. Human ERVs (HERVs) make up roughly 8.3% of the genome and over the course of evolution, HERV elements underwent positive selection and accrued mutations [...] Read more.

Endogenous retroviruses (ERVs), or LTR retrotransposons, are a class of transposable elements that are highly represented in mammalian genomes. Human ERVs (HERVs) make up roughly 8.3% of the genome and over the course of evolution, HERV elements underwent positive selection and accrued mutations that rendered them non-infectious; thereby, the genome could co-opt them into constructive roles with important biological functions. In the past two decades, with the help of advances in sequencing technology, ERVs are increasingly considered to be important components of the innate immune response. While typically silenced, expression of HERVs can be induced in response to traumatic, toxic, or infection-related stress, leading to a buildup of viral transcripts and under certain circumstances, proteins, including functionally active reverse transcriptase and viral envelopes. The biological activity of HERVs in the context of the innate immune response can be based on the functional effect of four major viral components: (1) HERV LTRs, (2) HERV-derived RNAs, (3) HERV-derived RNA:DNA duplexes and cDNA, and (4) HERV-derived proteins and ribonucleoprotein complexes. In this review, we will discuss the implications of HERVs in all four contexts in relation to innate immunity and their association with various pathological disease states. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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17 pages, 904 KiB

Open AccessEditor’s ChoiceReview

Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

by Dvir Gatt, Isaac Martin, Rawan AlFouzan and Theo J. Moraes

Pathogens 2023, 12(2), 154; https://doi.org/10.3390/pathogens12020154 - 17 Jan 2023

Cited by 16 | Viewed by 11130

Abstract

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease, especially in young children. Despite its global impact on healthcare, related to its high prevalence and its association with significant morbidity, the current therapy is still mostly supportive. Moreover, [...] Read more.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease, especially in young children. Despite its global impact on healthcare, related to its high prevalence and its association with significant morbidity, the current therapy is still mostly supportive. Moreover, while more than 50 years have passed since the first trial of an RSV vaccine (which unfortunately caused enhanced RSV disease), no vaccine has been approved for RSV prevention. In the last two decades, our understanding of the pathogenesis and immunopathology of RSV have continued to evolve, leading to significant advancements in RSV prevention strategies. These include both the development of new potential vaccines and the successful implementation of passive immunization, which, together, will provide coverage from infancy to old age. In this review, we provide an update of the current treatment options for acute disease (RSV-specific and -non-specific) and different therapeutic approaches focusing on RSV prevention. Full article

(This article belongs to the Special Issue The Changing Landscape of Respiratory Syncytial Virus Infections)

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20 pages, 2889 KiB

Open AccessEditor’s ChoiceArticle

Fusarium Yellows of Ginger (Zingiber officinale Roscoe) Caused by Fusarium oxysporum f. sp. zingiberi Is Associated with Cultivar-Specific Expression of Defense-Responsive Genes

by Duraisamy Prasath, Andrea Matthews, Wayne T. O’Neill, Elizabeth A. B. Aitken and Andrew Chen

Pathogens 2023, 12(1), 141; https://doi.org/10.3390/pathogens12010141 - 14 Jan 2023

Cited by 6 | Viewed by 2897

Abstract

Ginger (Zingiber officinale Roscoe) is an important horticultural crop, valued for its culinary and medicinal properties. Fusarium yellows of ginger, caused by Fusarium oxysporum f. sp. zingiberi (Foz), is a devastating disease that has significantly reduced the quality and crop [...] Read more.

Ginger (Zingiber officinale Roscoe) is an important horticultural crop, valued for its culinary and medicinal properties. Fusarium yellows of ginger, caused by Fusarium oxysporum f. sp. zingiberi (Foz), is a devastating disease that has significantly reduced the quality and crop yield of ginger worldwide. The compatible interaction between ginger and Foz leading to susceptibility is dissected here. The pathogenicity of two Foz isolates on ginger was confirmed by their ability to colonise ginger and in turn induce both internal and external plant symptoms typical of Fusarium yellows. To shed light on Foz susceptibility at the molecular level, a set of defense-responsive genes was analysed for expression in the roots of ginger cultivars challenged with Foz. These include nucleotide-binding site (NBS) type of resistant (R) genes with a functional role in pathogen recognition, transcription factors associated with systemic acquired resistance, and enzymes involved in terpenoid biosynthesis and cell wall modifications. Among three R genes, the transcripts of ZoNBS1 and ZoNBS3 were rapidly induced by Foz at the onset of infection, and the expression magnitude was cultivar-dependent. These expression characteristics extend to the other genes. This study is the first step in understanding the mechanisms of compatible host–pathogen interactions in ginger. Full article

(This article belongs to the Special Issue Current Research on Fusarium)

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15 pages, 1257 KiB

Open AccessEditor’s ChoiceReview

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development

by Christin Schmidt and Barbara S. Schnierle

Pathogens 2023, 12(1), 138; https://doi.org/10.3390/pathogens12010138 - 13 Jan 2023

Cited by 16 | Viewed by 12061

Abstract

The present use of mRNA vaccines against COVID-19 has shown for the first time the potential of mRNA vaccines for infectious diseases. Here we will summarize the current knowledge about improved mRNA vaccines, i.e., the self-amplifying mRNA (saRNA) vaccines. This approach may enhance [...] Read more.

The present use of mRNA vaccines against COVID-19 has shown for the first time the potential of mRNA vaccines for infectious diseases. Here we will summarize the current knowledge about improved mRNA vaccines, i.e., the self-amplifying mRNA (saRNA) vaccines. This approach may enhance antigen expression by amplification of the antigen-encoding RNA. RNA design, RNA delivery, and the innate immune responses induced by RNA will be reviewed. Full article

(This article belongs to the Special Issue Infectious Diseases and Vaccine Technology Research)

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24 pages, 392 KiB

Open AccessEditor’s ChoiceReview

Molecular Targets for Foodborne Pathogenic Bacteria Detection

by Spiros Paramithiotis

Pathogens 2023, 12(1), 104; https://doi.org/10.3390/pathogens12010104 - 08 Jan 2023

Cited by 2 | Viewed by 3092

Abstract

The detection of foodborne pathogenic bacteria currently relies on their ability to grow on chemically defined liquid and solid media, which is the essence of the classical microbiological approach. Such procedures are time-consuming and the quality of the result is affected by the [...] Read more.

The detection of foodborne pathogenic bacteria currently relies on their ability to grow on chemically defined liquid and solid media, which is the essence of the classical microbiological approach. Such procedures are time-consuming and the quality of the result is affected by the selectivity of the media employed. Several alternative strategies based on the detection of molecular markers have been proposed. These markers may be cell constituents, may reside on the cell envelope or may be specific metabolites. Each marker provides specific advantages and, at the same time, suffers from specific limitations. The food matrix and chemical composition, as well as the accompanying microbiota, may also severely compromise detection. The aim of the present review article is to present and critically discuss all available information regarding the molecular targets that have been employed as markers for the detection of foodborne pathogens. Their strengths and limitations, as well as the proposed alleviation strategies, are presented, with particular emphasis on their applicability in real food systems and the challenges that are yet to be effectively addressed. Full article

(This article belongs to the Special Issue 10th Anniversary of Pathogens—Feature Papers)

28 pages, 7699 KiB

Open AccessEditor’s ChoiceArticle

Genomics of Tenacibaculum Species in British Columbia, Canada

by Joseph P. Nowlan, Ashton N. Sies, Scott R. Britney, Andrew D. S. Cameron, Ahmed Siah, John S. Lumsden and Spencer Russell

Pathogens 2023, 12(1), 101; https://doi.org/10.3390/pathogens12010101 - 06 Jan 2023

Cited by 4 | Viewed by 2426

Abstract

Tenacibaculum is a genus of Gram-negative filamentous bacteria with a cosmopolitan distribution. The research describing Tenacibaculum genomes stems primarily from Norway and Chile due to their impacts on salmon aquaculture. Canadian salmon aquaculture also experiences mortality events related to the presence of Tenacibaculum [...] Read more.

Tenacibaculum is a genus of Gram-negative filamentous bacteria with a cosmopolitan distribution. The research describing Tenacibaculum genomes stems primarily from Norway and Chile due to their impacts on salmon aquaculture. Canadian salmon aquaculture also experiences mortality events related to the presence of Tenacibaculum spp., yet no Canadian Tenacibaculum genomes are publicly available. Ribosomal DNA sequencing of 16S and four species-specific 16S quantitative-PCR assays were used to select isolates cultured from Atlantic salmon with mouthrot in British Columbia (BC), Canada. Ten isolates representing four known and two unknown species of Tenacibaculum were selected for shotgun whole genome sequencing using the Oxford Nanopore’s MinION platform. The genome assemblies achieved closed circular chromosomes for seven isolates and long contigs for the remaining three isolates. Average nucleotide identity analysis identified T. ovolyticum, T. maritimum, T. dicentrarchi, two genomovars of T. finnmarkense, and two proposed novel species T. pacificus sp. nov. type strain 18-2881-A^T and T. retecalamus sp. nov. type strain 18-3228-7B^T. Annotation in most of the isolates predicted putative virulence and antimicrobial resistance genes, most-notably toxins (i.e., hemolysins), type-IX secretion systems, and oxytetracycline resistance. Comparative analysis with the T. maritimum type-strain predicted additional toxins and numerous C-terminal secretion proteins, including an M12B family metalloprotease in the T. maritimum isolates from BC. The genomic prediction of virulence-associated genes provides important targets for studies of mouthrot disease, and the annotation of the antimicrobial resistance genes provides targets for surveillance and diagnosis in veterinary medicine. Full article

(This article belongs to the Special Issue Emerging Infections in Aquatic Animals)

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17 pages, 1878 KiB

Open AccessEditor’s ChoiceArticle

Systematic Review and Modelling of Age-Dependent Prevalence of Toxoplasma gondii in Livestock, Wildlife and Felids in Europe

by Filip Dámek, Arno Swart, Helga Waap, Pikka Jokelainen, Delphine Le Roux, Gunita Deksne, Huifang Deng, Gereon Schares, Anna Lundén, Gema Álvarez-García, Martha Betson, Rebecca K. Davidson, Adriana Györke, Daniela Antolová, Zuzana Hurníková, Henk J. Wisselink, Jacek Sroka, Joke W. B. van der Giessen, Radu Blaga and Marieke Opsteegh

Pathogens 2023, 12(1), 97; https://doi.org/10.3390/pathogens12010097 - 06 Jan 2023

Cited by 12 | Viewed by 4045

Abstract

Toxoplasma gondii is a zoonotic parasite of importance to both human and animal health. The parasite has various transmission routes, and the meat of infected animals appears to be a major source of human infections in Europe. We aimed to estimate T. gondii [...] Read more.

Toxoplasma gondii is a zoonotic parasite of importance to both human and animal health. The parasite has various transmission routes, and the meat of infected animals appears to be a major source of human infections in Europe. We aimed to estimate T. gondii prevalence in a selection of animal host species. A systematic literature review resulting in 226 eligible publications was carried out, and serological data were analyzed using an age-dependent Bayesian hierarchical model to obtain estimates for the regional T. gondii seroprevalence in livestock, wildlife, and felids. Prevalence estimates varied between species, regions, indoor/outdoor rearing, and types of detection methods applied. The lowest estimated seroprevalence was observed for indoor-kept lagomorphs at 4.8% (95% CI: 1.8–7.5%) and the highest for outdoor-kept sheep at 63.3% (95% CI: 53.0–79.3%). Overall, T. gondii seroprevalence estimates were highest within Eastern Europe, whilst being lowest in Northern Europe. Prevalence data based on direct detection methods were scarce and were not modelled but rather directly summarized by species. The outcomes of the meta-analysis can be used to extrapolate data to areas with a lack of data and provide valuable inputs for future source attribution approaches aiming to estimate the relative contribution of different sources of T. gondii human infection. Full article

(This article belongs to the Special Issue Epidemiology and Management of Foodborne Parasitic Diseases)

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18 pages, 963 KiB

Open AccessEditor’s ChoiceArticle

Risk Factors for Exposure of Wild Birds to West Nile Virus in A Gradient of Wildlife-Livestock Interaction

by Laia Casades-Martí, Rocío Holgado-Martín, Pilar Aguilera-Sepúlveda, Francisco Llorente, Elisa Pérez-Ramírez, Miguel Ángel Jiménez-Clavero and Francisco Ruiz-Fons

Pathogens 2023, 12(1), 83; https://doi.org/10.3390/pathogens12010083 - 03 Jan 2023

Cited by 6 | Viewed by 2524

Abstract

West Nile virus (WNV) transmission rate is shaped by the interaction between virus reservoirs and vectors, which may be maximized in farm environments. Based on this hypothesis, we screened for WNV in wild birds in three scenarios with decreasing gradient of interaction with [...] Read more.

West Nile virus (WNV) transmission rate is shaped by the interaction between virus reservoirs and vectors, which may be maximized in farm environments. Based on this hypothesis, we screened for WNV in wild birds in three scenarios with decreasing gradient of interaction with horses: (i) the farm (A₁); (ii) the neighborhood (A₂); and (iii) a wild area (A₃). We captured wild birds and analyzed their sera for WNV antibodies by blocking ELISA and micro-virus neutralization test. Flavivirus infections were tested with generic and specific PCR protocols. We parameterized linear mixed models with predictors (bird abundance and diversity, vector abundance, vector host abundance, and weather quantities) to identify Flavivirus spp. and WNV exposure risk factors. We detected a low rate of Flavivirus infections by PCR (0.8%) and 6.9% of the birds were seropositive by ELISA. Exposure to Flavivirus spp. was higher in A₁ (9%) than in A₂ and A₃ (5.6% and 5.8%, respectively). Bird diversity was the most relevant predictor of exposure risk and passerines dominated the on-farm bird community. Our results suggest that measures deterring the use of the farm by passerines should be implemented because the environmental favorability of continental Mediterranean environments for WNV is increasing and more outbreaks are expected. Full article

(This article belongs to the Special Issue Surveillance of Zoonotic Pathogens Carried by Wildlife)

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15 pages, 2022 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of Escherichia coli Pathotypes in Diarrheic Calves in a Low-Income Setting

by Wagaw Sendeku Chekole, Haileeyesus Adamu, Susanna Sternberg-Lewrein, Ulf Magnusson and Tesfaye Sisay Tessema

Pathogens 2023, 12(1), 42; https://doi.org/10.3390/pathogens12010042 - 27 Dec 2022

Cited by 3 | Viewed by 2487

Abstract

Different E. coli pathotypes are common zoonotic agents. Some of these pathotypes cause recurrent and widespread calf diarrhea and contribute to significant economic losses in the livestock sector worldwide in addition to putting humans at risk. Here, we investigated the occurrence of E. [...] Read more.

Different E. coli pathotypes are common zoonotic agents. Some of these pathotypes cause recurrent and widespread calf diarrhea and contribute to significant economic losses in the livestock sector worldwide in addition to putting humans at risk. Here, we investigated the occurrence of E. coli pathotypes in diarrheic calves in Ethiopia kept under various calf management practices. One hundred fecal samples were collected from diarrheic calves in 98 different farms. E. coli was isolated in the samples from 99 of the diarrheic calves, and virulence genes were detected in 80% of the samples. The occurrence of E. coli pathotypes in the samples was 32% ETEC, 23% STEC, 18% STEC/ETEC, 3% EPEC, 2% EAEC, and 1% EHEC. No diarrheic calves were positive for the EIEC and DAEC pathotypes. The occurrence of pathotypes was positively associated with female calves (EPEC, p = 0.006), aged less than 2 weeks (STEC, p = 0.059), and calves fed colostrum via the hand method (STEC, p = 0.008 and EAEC, p = 0.003). This study revealed that several E. coli pathotypes occurred among calves affected with diarrhea. Moreover, the presence of a mixed STEC/ETEC pathotypes infection was present in the studied low-income setting. These findings indicate a considerable risk for the zoonotic transmission from calves to humans and the options to provide the better management for younger calves in order to reduce the economic loss. Full article

(This article belongs to the Section Bacterial Pathogens)

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18 pages, 8135 KiB

Open AccessEditor’s ChoiceArticle

Genomic Analysis Unveils the Pervasiveness and Diversity of Prophages Infecting Erwinia Species

by Tulio Morgan, Rafael Reis de Rezende, Thamylles Thuany Mayrink Lima, Flávia de Oliveira Souza and Poliane Alfenas-Zerbini

Pathogens 2023, 12(1), 44; https://doi.org/10.3390/pathogens12010044 - 27 Dec 2022

Cited by 1 | Viewed by 3210

Abstract

Prophages are abundant elements integrated into bacterial genomes and contribute to inter-strain genetic variability and, in some cases, modulate the environmental behavior of bacteria, such as pathogen virulence. Here, we described prophage occurrence and diversity in publicly available Erwinia genome assemblies, a genus [...] Read more.

Prophages are abundant elements integrated into bacterial genomes and contribute to inter-strain genetic variability and, in some cases, modulate the environmental behavior of bacteria, such as pathogen virulence. Here, we described prophage occurrence and diversity in publicly available Erwinia genome assemblies, a genus containing plant pathogens. Prophage-like sequences were identified and taxonomically classified. Sequence diversity was analyzed through intergenomic similarities. Furthermore, we searched for anti-phage defense systems in Erwinia spp., such as DISARM, BREX, and CRISPR-Cas systems, and identified the putative targets of CRISPR spacers. We identified 939 prophage-like sequences in 221 Erwinia spp. genome assemblies. Only 243 prophage-like sequences were classified, all belonging to the Caudoviricetes class. The set of putative Erwinia prophages was mostly unique since only three sequences showed more than 70% intergenomic similarities to known Erwinia phages. Overall, the number and type of CRISPR-Cas systems were conserved within Erwinia species, with many spacers directed to the putative prophages identified. This study increased the knowledge of the diversity and distribution of Erwinia prophages, contributing to the characterization of genetic and ecological factors influencing Erwinia spp. environmental fitness. Full article

(This article belongs to the Special Issue Viruses of Microbes: From Basics to Biotechnological Application)

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18 pages, 986 KiB

Open AccessEditor’s ChoiceReview

The Use of Natural Methods to Control Foodborne Biofilms

by Michelle Marie Esposito and Sara Turku

Pathogens 2023, 12(1), 45; https://doi.org/10.3390/pathogens12010045 - 27 Dec 2022

Cited by 7 | Viewed by 2730

Abstract

Biofilms are large aggregates of various species of bacteria or other microorganisms tightly attached to surfaces through an intricate extracellular matrix. These complex microbial communities present quite the challenge in the food processing industry, as conditions such as raw meats and diverse food [...] Read more.

Biofilms are large aggregates of various species of bacteria or other microorganisms tightly attached to surfaces through an intricate extracellular matrix. These complex microbial communities present quite the challenge in the food processing industry, as conditions such as raw meats and diverse food product content in contact with workers, drains, machinery, and ventilation systems, make for prime circumstances for contamination. Adding to the challenge is the highly resistant nature of these biofilm growths and the need to keep in mind that any antimicrobials utilized in these situations risk health implications with human consumption of the products that are being processed in these locations. For that reason, the ideal means of sanitizing areas of foodborne biofilms would be natural means. Herein, we review a series of innovative natural methods of targeting foodborne biofilms, including bacteriocins, bacteriophages, fungi, phytochemicals, plant extracts, essential oils, gaseous and aqueous control, photocatalysis, enzymatic treatments, and ultrasound mechanisms. Full article

(This article belongs to the Special Issue Foodborne Pathogen Biofilms: Development, Detection, Control, and Antimicrobial Resistance)

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19 pages, 1587 KiB

Open AccessEditor’s ChoiceReview

Many Ways to Communicate—Crosstalk between the HBV-Infected Cell and Its Environment

by Annika Jasmin Walter, Maarten A. van de Klundert and Stephanie Jung

Pathogens 2023, 12(1), 29; https://doi.org/10.3390/pathogens12010029 - 24 Dec 2022

Cited by 1 | Viewed by 2626

Abstract

Chronic infection with the hepatitis B virus (HBV) affects an estimated 257 million people worldwide and can lead to liver diseases such as cirrhosis and liver cancer. Viral replication is generally considered not to be cytopathic, and although some HBV proteins may have [...] Read more.

Chronic infection with the hepatitis B virus (HBV) affects an estimated 257 million people worldwide and can lead to liver diseases such as cirrhosis and liver cancer. Viral replication is generally considered not to be cytopathic, and although some HBV proteins may have direct carcinogenic effects, the majority of HBV infection-related disease is related to chronic inflammation resulting from disrupted antiviral responses and aberrant innate immune reactions. Like all cells, healthy and HBV-infected cells communicate with each other, as well as with other cell types, such as innate and adaptive immune cells. They do so by both interacting directly and by secreting factors into their environment. Such factors may be small molecules, such as metabolites, single viral proteins or host proteins, but can also be more complex, such as virions, protein complexes, and extracellular vesicles. The latter are small, membrane-enclosed vesicles that are exchanged between cells, and have recently gained a lot of attention for their potential to mediate complex communication and their potential for therapeutic repurposing. Here, we review how HBV infection affects the communication between HBV-infected cells and cells in their environment. We discuss the impact of these interactions on viral persistence in chronic infection, as well as their relation to HBV infection-related pathology. Full article

(This article belongs to the Special Issue 10th Anniversary of Pathogens—Emerging and Re-emerging Viral Pathogens in a Pandemic World)

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13 pages, 1496 KiB

Open AccessEditor’s ChoiceReview

The Never-Ending Presence of Phytophthora Species in Italian Nurseries

by Chiara Antonelli, Margherita Biscontri, Dania Tabet and Anna Maria Vettraino

Pathogens 2023, 12(1), 15; https://doi.org/10.3390/pathogens12010015 - 22 Dec 2022

Cited by 8 | Viewed by 2954

Abstract

Plant trade coupled with climate change has led to the increased spread of well-known and new Phytophthora species, a group of fungus-like organisms placed in the Kingdom Chromista. Their presence in plant nurseries is of particular concern because they are responsible for many [...] Read more.

Plant trade coupled with climate change has led to the increased spread of well-known and new Phytophthora species, a group of fungus-like organisms placed in the Kingdom Chromista. Their presence in plant nurseries is of particular concern because they are responsible for many plant diseases, with high environmental, economic and social impacts. This paper offers a brief overview of the current status of Phytophthora species in European plant nurseries. Focus was placed on Italian sites. Despite the increasing awareness of the risk of Phytophthora spread and the management strategies applied for controlling it, the complexity of the Phytophthora community in the horticulture industry is increasing over time. Since the survey carried out by Jung et al. (2016), new Phytophthora taxa and Phytophthora-host associations were identified. Phytophthorahydropathica, P. crassamura, P. pseudocryptogea and P. meadii were reported for the first time in European plant nurseries, while P. pistaciae, P. mediterranea and P. heterospora were isolated from Italian ornamental nurseries. Knowledge of Phytophthora diversity in plant nurseries and the potential damage caused by them will help to contribute to the development of early detection methods and sustainable management strategies to control Phytophthora spread in the future. Full article

(This article belongs to the Special Issue Advances and Challenges in Understanding and Management of Diseases Caused by Oomycetes)

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13 pages, 3277 KiB

Open AccessEditor’s ChoiceReview

The History of the Intestinal Microbiota and the Gut-Brain Axis

by Zuzanna Lewandowska-Pietruszka, Magdalena Figlerowicz and Katarzyna Mazur-Melewska

Pathogens 2022, 11(12), 1540; https://doi.org/10.3390/pathogens11121540 - 15 Dec 2022

Cited by 5 | Viewed by 4161

Abstract

The gut-brain axis and the intestinal microbiota have been an area of an intensive research in the last few years. However, it is not a completely novel area of interest for physicians and scientists. From the earliest centuries, both professionals and patients turned [...] Read more.

The gut-brain axis and the intestinal microbiota have been an area of an intensive research in the last few years. However, it is not a completely novel area of interest for physicians and scientists. From the earliest centuries, both professionals and patients turned their attention to the gastrointestinal system in order to find the root of physical and mental disturbances. The approach to the gut-brain axis and the therapeutic methods have changed alongside the development of different medical approaches to health and illness. They often reflected the social changes. The authors of this article aim to provide a brief history of the gut-brain axis and the intestinal microbiota in order to demonstrate how important the study of these systems is for both scientists and medical professionals, as well as for the general public. We analysed the publications accessible through PubMed regarding the microbiota and gut-brain axis history. If available, we accessed the original historical sources. We conclude that although the history of this science might be long, there are still many areas that need to be researched, analysed, and understood in future projects. The interest in the subject is not diminishing, but rather it has increased throughout the years. Full article

(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)

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18 pages, 2263 KiB

Open AccessEditor’s ChoiceArticle

Artificial Insemination as an Alternative Transmission Route for African Swine Fever Virus

by Virginia Friedrichs, Darwin Reicks, Tobias Hasenfuß, Elisabeth Gerstenkorn, Jeffrey J. Zimmerman, Eric A. Nelson, Tessa Carrau, Paul Deutschmann, Julia Sehl-Ewert, Hanna Roszyk, Martin Beer, Jane Christopher-Hennings and Sandra Blome

Pathogens 2022, 11(12), 1539; https://doi.org/10.3390/pathogens11121539 - 14 Dec 2022

Cited by 4 | Viewed by 6599

Abstract

The rapid spread of the African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries worldwide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, [...] Read more.

The rapid spread of the African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries worldwide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, alternative transmission routes for ASFV have yet to be assessed. Here, we demonstrate that ASFV can efficiently be transferred from infected boars to naïve recipient gilts through artificial insemination (AI). In modern pig production, semen from boar studs often supplies many sow herds. Thus, the infection of a boar stud presents the risk of rapidly and widely distributing ASFV within or between countries. Daily blood and semen collection from four boars after intramuscular inoculation with ASFV strain ‘Estonia 2014’ resulted in the detection of ASFV genomes in the semen as early as 2 dpi, in blood at 1 dpi while semen quality remained largely unaffected. Ultimately, after insemination with extended semen, 7 of 14 gilts were ASFV positive by 7 days post insemination, and all gilts were ASFV positive by 35 days post insemination. Twelve out of 13 pregnant gilts aborted or resorbed at the onset of fever. A proportion of fetuses originating from the remaining gilt showed both abnormalities and replication of ASFV in fetal tissues. Thus, we present evidence for the efficient transmission of ASFV to gilts via AI and also to implanted embryos. These results underline the critical role that boar semen could play in ASFV transmission. Full article

(This article belongs to the Special Issue An Update on African Swine Fever)

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13 pages, 3082 KiB

Open AccessEditor’s ChoiceArticle

Monitoring Wind-Borne Particle Matter Entering Poultry Farms via the Air-Inlet: Highly Pathogenic Avian Influenza Virus and Other Pathogens Risk

by Armin R. W. Elbers, José L. Gonzales, Miriam G. J. Koene, Evelien A. Germeraad, Renate W. Hakze-van der Honing, Marleen van der Most, Henk Rodenboog and Francisca C. Velkers

Pathogens 2022, 11(12), 1534; https://doi.org/10.3390/pathogens11121534 - 14 Dec 2022

Cited by 5 | Viewed by 3481

Abstract

Wind-supported transport of particle matter (PM) contaminated with excreta from highly pathogenic avian influenza virus (HPAIv)-infected wild birds may be a HPAIv-introduction pathway, which may explain infections in indoor-housed poultry. The primary objective of our study was therefore to measure the nature and [...] Read more.

Wind-supported transport of particle matter (PM) contaminated with excreta from highly pathogenic avian influenza virus (HPAIv)-infected wild birds may be a HPAIv-introduction pathway, which may explain infections in indoor-housed poultry. The primary objective of our study was therefore to measure the nature and quantity of PM entering poultry houses via air-inlets. The air-inlets of two recently HPAIv-infected poultry farms (a broiler farm and a layer farm) were equipped with mosquito-net collection bags. PM was harvested every 5 days for 25 days. Video-camera monitoring registered wild bird visits. PM was tested for avian influenza viruses (AIV), Campylobacter and Salmonella with PCR. Insects, predominantly mosquitoes, were tested for AIV, West Nile, Usutu and Schmallenberg virus. A considerable number of mosquitoes and small PM amounts entered the air-inlets, mostly cobweb and plant material, but no wild bird feathers. Substantial variation in PM entering between air-inlets existed. In stormy periods, significantly larger PM amounts may enter wind-directed air-inlets. PM samples were AIV and Salmonella negative and insect samples were negative for all viruses and bacteria, but several broiler and layer farm PM samples tested Campylobacter positive. Regular wild (water) bird visits were observed near to the poultry houses. Air-borne PM and insects—potentially contaminated with HPAIv or other pathogens—can enter poultry air-inlets. Implementation of measures limiting this potential introduction route are recommended. Full article

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22 pages, 345 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Approaches for Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

by Yehudis Rosenwasser, Irene Berger and Zvi G. Loewy

Pathogens 2022, 11(12), 1513; https://doi.org/10.3390/pathogens11121513 - 10 Dec 2022

Cited by 7 | Viewed by 2842

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a progressive pulmonary disorder underpinned by poorly reversible airflow resulting from chronic bronchitis or emphysema. The prevalence and mortality of COPD continue to increase. Pharmacotherapy for patients with COPD has included antibiotics, bronchodilators, and anti-inflammatory corticosteroids (but [...] Read more.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive pulmonary disorder underpinned by poorly reversible airflow resulting from chronic bronchitis or emphysema. The prevalence and mortality of COPD continue to increase. Pharmacotherapy for patients with COPD has included antibiotics, bronchodilators, and anti-inflammatory corticosteroids (but with little success). Oral diseases have long been established as clinical risk factors for developing respiratory diseases. The establishment of a very similar microbiome in the mouth and the lung confirms the oral-lung connection. The aspiration of pathogenic microbes from the oral cavity has been implicated in several respiratory diseases, including pneumonia and chronic obstructive pulmonary disease (COPD). This review focuses on current and future pharmacotherapeutic approaches for COPD exacerbation including antimicrobials, mucoregulators, the use of bronchodilators and anti-inflammatory drugs, modifying epigenetic marks, and modulating dysbiosis of the microbiome. Full article

(This article belongs to the Section Bacterial Pathogens)

12 pages, 600 KiB

Open AccessEditor’s ChoiceArticle

Characteristics of Staphylococcus aureus Isolated from Patients in Busia County Referral Hospital, Kenya

by Benear Apollo Obanda, Elizabeth A. J. Cook, Eric M. Fèvre, Lilly Bebora, William Ogara, Shu-Hua Wang, Wondwossen Gebreyes, Ronald Ngetich, Dolphine Wandede, Johnstone Muyodi, Beth Blane, Francesc Coll, Ewan M. Harrison, Sharon J. Peacock and George C. Gitao

Pathogens 2022, 11(12), 1504; https://doi.org/10.3390/pathogens11121504 - 09 Dec 2022

Cited by 3 | Viewed by 2054

Abstract

Staphylococcus aureus is an important pathogen associated with hospital, community, and livestock-acquired infections, with the ability to develop resistance to antibiotics. Nasal carriage by hospital inpatients is a risk for opportunistic infections. Antibiotic susceptibility patterns, virulence genes and genetic population structure of S. [...] Read more.

Staphylococcus aureus is an important pathogen associated with hospital, community, and livestock-acquired infections, with the ability to develop resistance to antibiotics. Nasal carriage by hospital inpatients is a risk for opportunistic infections. Antibiotic susceptibility patterns, virulence genes and genetic population structure of S. aureus nasal isolates, from inpatients at Busia County Referral Hospital (BCRH) were analyzed. A total of 263 inpatients were randomly sampled, from May to July 2015. The majority of inpatients (85.9%) were treated empirically with antimicrobials, including ceftriaxone (65.8%) and metronidazole (49.8%). Thirty S. aureus isolates were cultured from 29 inpatients with a prevalence of 11% (10.3% methicillin-susceptible S. aureus (MSSA), 0.8% methicillin resistant S. aureus (MRSA)). Phenotypic and genotypic resistance was highest to penicillin-G (96.8%), trimethoprim (73.3%), and tetracycline (13.3%) with 20% of isolates classified as multidrug resistant. Virulence genes, Panton-Valentine leukocidin (pvl), toxic shock syndrome toxin-1 (tsst-1), and sasX gene were detected in 16.7%, 23.3% and 3.3% of isolates. Phylogenetic analysis showed 4 predominant clonal complexes CC152, CC8, CC80, and CC508. This study has identified that inpatients of BCRH were carriers of S. aureus harbouring virulence genes and resistance to a range of antibiotics. This may indicate a public health risk to other patients and the community. Full article

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12 pages, 652 KiB

Open AccessEditor’s ChoiceArticle

Whole-Genome Sequencing of Six Neglected Arboviruses Circulating in Africa Using Sequence-Independent Single Primer Amplification (SISPA) and MinION Nanopore Technologies

by Ansgar Schulz, Balal Sadeghi, Franziska Stoek, Jacqueline King, Kerstin Fischer, Anne Pohlmann, Martin Eiden and Martin H. Groschup

Pathogens 2022, 11(12), 1502; https://doi.org/10.3390/pathogens11121502 - 08 Dec 2022

Cited by 2 | Viewed by 2110

Abstract

On the African continent, a large number of arthropod-borne viruses (arboviruses) with zoonotic potential have been described, and yet little is known of most of these pathogens, including their actual distribution or genetic diversity. In this study, we evaluated as a proof-of-concept the [...] Read more.

On the African continent, a large number of arthropod-borne viruses (arboviruses) with zoonotic potential have been described, and yet little is known of most of these pathogens, including their actual distribution or genetic diversity. In this study, we evaluated as a proof-of-concept the effectiveness of the nonspecific sequencing technique sequence-independent single primer amplification (SISPA) on third-generation sequencing techniques (MinION sequencing, Oxford Nanopore Technologies, Oxford, UK) by comparing the sequencing results from six different samples of arboviruses known to be circulating in Africa (Crimean–Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), Dugbe virus (DUGV), Nairobi sheep disease virus (NSDV), Middleburg virus (MIDV) and Wesselsbron virus (WSLV)). All sequenced samples were derived either from previous field studies or animal infection trials. Using this approach, we were able to generate complete genomes for all six viruses without the need for virus-specific whole-genome PCRs. Higher Cq values in diagnostic RT-qPCRs and the origin of the samples (from cell culture or animal origin) along with their quality were found to be factors affecting the success of the sequencing run. The results of this study may stimulate the use of metagenomic sequencing approaches, contributing to a better understanding of the genetic diversity of neglected arboviruses. Full article

(This article belongs to the Special Issue Molecular Diagnostics of Emerging Pathogens)

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25 pages, 810 KiB

Open AccessEditor’s ChoiceReview

Listeria monocytogenes—How This Pathogen Uses Its Virulence Mechanisms to Infect the Hosts

by Jacek Osek and Kinga Wieczorek

Pathogens 2022, 11(12), 1491; https://doi.org/10.3390/pathogens11121491 - 07 Dec 2022

Cited by 14 | Viewed by 5667

Abstract

Listeriosis is a serious food-borne illness, especially in susceptible populations, including children, pregnant women, and elderlies. The disease can occur in two forms: non-invasive febrile gastroenteritis and severe invasive listeriosis with septicemia, meningoencephalitis, perinatal infections, and abortion. Expression of each symptom depends on [...] Read more.

Listeriosis is a serious food-borne illness, especially in susceptible populations, including children, pregnant women, and elderlies. The disease can occur in two forms: non-invasive febrile gastroenteritis and severe invasive listeriosis with septicemia, meningoencephalitis, perinatal infections, and abortion. Expression of each symptom depends on various bacterial virulence factors, immunological status of the infected person, and the number of ingested bacteria. Internalins, mainly InlA and InlB, invasins (invasin A, LAP), and other surface adhesion proteins (InlP1, InlP4) are responsible for epithelial cell binding, whereas internalin C (InlC) and actin assembly-inducing protein (ActA) are involved in cell-to-cell bacterial spread. L. monocytogenes is able to disseminate through the blood and invade diverse host organs. In persons with impaired immunity, the elderly, and pregnant women, the pathogen can also cross the blood–brain and placental barriers, which results in the invasion of the central nervous system and fetus infection, respectively. The aim of this comprehensive review is to summarize the current knowledge on the epidemiology of listeriosis and L. monocytogenes virulence mechanisms that are involved in host infection, with a special focus on their molecular and cellular aspects. We believe that all this information is crucial for a better understanding of the pathogenesis of L. monocytogenes infection. Full article

(This article belongs to the Section Bacterial Pathogens)

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21 pages, 2131 KiB

Open AccessEditor’s ChoiceReview

Giant Viruses as a Source of Novel Enzymes for Biotechnological Application

by Ellen Gonçalves de Oliveira, João Victor Rodrigues Pessoa Carvalho, Bruna Barbosa Botelho, Clécio Alonso da Costa Filho, Lethícia Ribeiro Henriques, Bruna Luiza de Azevedo and Rodrigo Araújo Lima Rodrigues

Pathogens 2022, 11(12), 1453; https://doi.org/10.3390/pathogens11121453 - 01 Dec 2022

Cited by 5 | Viewed by 2352

Abstract

The global demand for industrial enzymes has been increasing in recent years, and the search for new sources of these biological products is intense, especially in microorganisms. Most known viruses have limited genetic machinery and, thus, have been overlooked by the enzyme industry [...] Read more.

The global demand for industrial enzymes has been increasing in recent years, and the search for new sources of these biological products is intense, especially in microorganisms. Most known viruses have limited genetic machinery and, thus, have been overlooked by the enzyme industry for years. However, a peculiar group of viruses breaks this paradigm. Giant viruses of the phylum Nucleocytoviricota infect protists (i.e., algae and amoebae) and have complex genomes, reaching up to 2.7 Mb in length and encoding hundreds of genes. Different giant viruses have robust metabolic machinery, especially those in the Phycodnaviridae and Mimiviridae families. In this review, we present some peculiarities of giant viruses that infect protists and discuss why they should be seen as an outstanding source of new enzymes. We revisited the genomes of representatives of different groups of giant viruses and put together information about their enzymatic machinery, highlighting several genes to be explored in biotechnology involved in carbohydrate metabolism, DNA replication, and RNA processing, among others. Finally, we present additional evidence based on structural biology using chitinase as a model to reinforce the role of giant viruses as a source of novel enzymes for biotechnological application. Full article

(This article belongs to the Special Issue Viruses of Microbes: From Basics to Biotechnological Application)

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30 pages, 1333 KiB

Open AccessEditor’s ChoiceReview

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems

by Ingrid Andrêssa de Moura, Anna Jéssica Duarte Silva, Larissa Silva de Macêdo, Maria da Conceição Viana Invenção, Mylenna Máyra Gois de Sousa and Antonio Carlos de Freitas

Pathogens 2022, 11(12), 1444; https://doi.org/10.3390/pathogens11121444 - 30 Nov 2022

Cited by 8 | Viewed by 2520

Abstract

Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on [...] Read more.

Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on nucleic acids are fast and simple approaches to eliciting adaptive immune responses. However, techniques to boost immunogenicity, reduce degradation, and facilitate their capture by immune cells are frequently required. One option to overcome this constraint is to employ delivery systems that allow selective antigen absorption and help modulate the immune response. This review aimed to discuss the influence of these different systems on the response generated by nucleic acid vaccines. The results indicate that delivery systems based on lipids, polymers, and microorganisms such as yeasts can be used to ensure the stability and transport of nucleic acid vaccines to their respective protein synthesis compartments. Thus, in view of the limitations of nucleic acid-based vaccines, it is important to consider the type of delivery system to be used—due to its impact on the immune response and desired final effect. Full article

(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)

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15 pages, 3495 KiB

Open AccessEditor’s ChoiceArticle

SARS-CoV-2 Antibody Effectiveness Is Influenced by Non-Epitope Mutation/Binding-Induced Denaturation of the Epitope 3D Architecture

by Moffat M. Malisheni, Matthew Bates, Albert A. Rizvanov and Paul A. MacAry

Pathogens 2022, 11(12), 1437; https://doi.org/10.3390/pathogens11121437 - 29 Nov 2022

Cited by 2 | Viewed by 1511

Abstract

The public health threat from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to intensify with emerging variants of concern (VOC) aiming to render COVID-19 vaccines/infection-induced antibodies redundant. The SARS-CoV-2 spike protein is responsible for receptor binding and infection of host cells making [...] Read more.

The public health threat from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to intensify with emerging variants of concern (VOC) aiming to render COVID-19 vaccines/infection-induced antibodies redundant. The SARS-CoV-2 spike protein is responsible for receptor binding and infection of host cells making it a legitimate antibody target. Antibodies mostly target epitopes in the receptor binding domain (RBD). Mutations occurring within epitopes influence antibody specificity and function by altering their 3D architecture. However, the mechanisms by which non-epitope mutations in the RBD influence antibody specificity and function remain a mystery. We used Protein Data Bank (PDB) deposited 3D structures for the original, Beta, Delta, BA.1, and BA.2 RBD proteins in complex with either neutralizing antibodies or Angiotensin-Converting Enzyme 2 (ACE2) to elucidate the structural and mechanistic basis for neutralizing antibody evasion driven by non-epitope amino acid substitutions in the RBD. Since the mechanism behind the extensively reported functional discrepancies between the same antibody when used individually and when used in an antibody cocktail is lacking, we explored the structural basis for this inconsistency. Finally, since SARS-CoV-2 antibodies are viral mutagens, we deciphered determinants for antibody-pressured amino acid substitutions. On the one hand, we show that non-epitope mutations in the RBD domain of SARS-CoV-2 VOC influence the formation of hydrogen bonds in the paratope-epitope interface by repositioning RBD amino-acid sidechains (AASCs). This increases the distance between complementary donor/acceptor atoms on paratope and epitope AASCs leading to weaker or the complete prevention of the formation of hydrogen bonds in the paratope-epitope interface. On the other hand, we show that SARS-CoV-2 VOC employ the same strategy to simultaneously search for complementary donor/acceptor atoms on ACE2 AASCs to form new interactions, potentially favoring increased viral transmission. Additionally, we illustrate that converting the spike protein to an RBD, a deletion mutation, also repositions epitope AASCs and that AASC interactions in the paratope-epitope interface vary when an antibody is used individually versus when utilized as a cocktail with other antibodies. Finally, we show that the process of substituting immunogenic RBD amino acids begins with the repositioning of their AASCs induced by immune/antibody pressure. We show that donor/acceptor atoms from any amino acid can determine cross-reactivity instead, provided they possess and present spatially pairing donor/acceptor atoms. By studying structural alignments for PDB deposited antibody-RBD 3D structures and relating them to published binding and neutralization profiles of the same antibodies, we demonstrate that minor structural alterations such as epitope AASC repositioning have a major impact on antibody effectiveness and, hence, should receive adequate attention given that protein structure dictates protein function. Full article

(This article belongs to the Collection Biomarkers and Pathogenesis of Infectious and Autoimmune Diseases)

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22 pages, 1348 KiB

Open AccessEditor’s ChoiceReview

The Tapeworm Hymenolepis diminuta as an Important Model Organism in the Experimental Parasitology of the 21st Century

by Anna Sulima-Celińska, Alicja Kalinowska and Daniel Młocicki

Pathogens 2022, 11(12), 1439; https://doi.org/10.3390/pathogens11121439 - 29 Nov 2022

Cited by 3 | Viewed by 4491

Abstract

The tapeworm Hymenolepis diminuta is a common parasite of the small intestine in rodents but it can also infect humans. Due to its characteristics and ease of maintenance in the laboratory, H. diminuta is also an important model species in studies of cestodiasis, [...] Read more.

The tapeworm Hymenolepis diminuta is a common parasite of the small intestine in rodents but it can also infect humans. Due to its characteristics and ease of maintenance in the laboratory, H. diminuta is also an important model species in studies of cestodiasis, including the search for new drugs, treatments, diagnostics and biochemical processes, as well as its host–parasite interrelationships. A great deal of attention has been devoted to the immune response caused by H. diminuta in the host, and several studies indicate that infection with H. diminuta can reduce the severity of concomitant disease. Here, we present a critical review of the experimental research conducted with the use of H. diminuta as a model organism for over more than two decades (in the 21st century). The present review evaluates the tapeworm H. diminuta as a model organism for studying the molecular biology, biochemistry and immunology aspects of parasitology, as well as certain clinical applications. It also systematizes the latest research on this species. Its findings may contribute to a better understanding of the biology of tapeworms and their adaptation to parasitism, including complex correlations between H. diminuta and invertebrate and vertebrate hosts. It places particular emphasis on its value for the further development of modern experimental parasitology. Full article

(This article belongs to the Special Issue Biology of Parasitism)

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19 pages, 1792 KiB

Open AccessEditor’s ChoiceReview

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

by Jianlin Lu, Jessica M. Gullett and Thirumala-Devi Kanneganti

Pathogens 2022, 11(12), 1400; https://doi.org/10.3390/pathogens11121400 - 23 Nov 2022

Cited by 5 | Viewed by 6949

Abstract

Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as [...] Read more.

Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics. Full article

(This article belongs to the Special Issue New Research on Filovirus Infections)

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22 pages, 8563 KiB

Open AccessEditor’s ChoiceArticle

Antagonistic Activity of Potentially Probiotic Lactic Acid Bacteria against Honeybee (Apis mellifera L.) Pathogens

by Aleksandra Leska, Adriana Nowak, Justyna Szulc, Ilona Motyl and Karolina Henryka Czarnecka-Chrebelska

Pathogens 2022, 11(11), 1367; https://doi.org/10.3390/pathogens11111367 - 16 Nov 2022

Cited by 5 | Viewed by 4762

Abstract

Lactic acid bacteria (LAB) are an essential part of the microbiota of the digestive tract of honeybees (Apis mellifera L.). Antagonistic activity of 103 LAB strains (isolates from different environments) against 21 honeybee pathogens/opportunistic pathogens (with agar slab method) was screened. The [...] Read more.

Lactic acid bacteria (LAB) are an essential part of the microbiota of the digestive tract of honeybees (Apis mellifera L.). Antagonistic activity of 103 LAB strains (isolates from different environments) against 21 honeybee pathogens/opportunistic pathogens (with agar slab method) was screened. The growth of Paenibacillus genus was inhibited to the most extent. The highest antagonistic activity was demonstrated by Lacticaseibacillus casei 12AN, while the lowest by Apilactobacillus kunkeei DSM 12361, a species naturally inhabiting the honeybee gut. LAB isolated from the honeybee environment demonstrated stronger antagonism against pathogens than collection strains. The antagonistic activity of cell-free supernatants (CFSs) from 24 LAB strains against 7 honeybee pathogens was additionally assessed at physiological pH with the microtitration method. The same was determined for selected CFSs at neutralized pH. CFSs with physiological pH showed significantly stronger antibacterial activity than CFSs with neutralized pH. The results confirmed that the mechanism of antimicrobial activity of LAB is acidification of the environment. The obtained results may, in the future, contribute to a better understanding of the antagonistic properties of LAB and the construction of a probiotic preparation to increase the viability of honeybee colonies. Full article

(This article belongs to the Special Issue Diseases of Insect Pollinators)

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17 pages, 3634 KiB

Open AccessEditor’s ChoiceArticle

Isolation of a New Infectious Pancreatic Necrosis Virus (IPNV) Variant from Genetically Resistant Farmed Atlantic Salmon (Salmo salar) during 2021–2022

by Marcos Godoy, Molly J. T. Kibenge, Marco Montes de Oca, Juan Pablo Pontigo, Yoandy Coca, Diego Caro, Karina Kusch, Rudy Suarez, Ian Burbulis and Frederick S. B. Kibenge

Pathogens 2022, 11(11), 1368; https://doi.org/10.3390/pathogens11111368 - 16 Nov 2022

Cited by 2 | Viewed by 3197

Abstract

Infectious pancreatic necrosis (IPN), caused by IPNV, affects several species of farmed fish, particularly Atlantic salmon, and is responsible for significant economic losses in salmon aquaculture globally. Despite the introduction of genetically resistant farmed Atlantic salmon and vaccination strategies in the Chilean salmon [...] Read more.

Infectious pancreatic necrosis (IPN), caused by IPNV, affects several species of farmed fish, particularly Atlantic salmon, and is responsible for significant economic losses in salmon aquaculture globally. Despite the introduction of genetically resistant farmed Atlantic salmon and vaccination strategies in the Chilean salmon industry since 2019, the number of IPN outbreaks has been increasing in farmed Atlantic salmon in the freshwater phase. This study examined gross and histopathological lesions of IPNV-affected fish, as well as the IPNV nucleotide sequence encoding the VP2 protein in clinical cases. The mortality reached 0.4% per day, and the cumulative mortality was from 0.4 to 3.5%. IPNV was isolated in the CHSE-214 cell line and was confirmed by RT-PCR, and VP2 sequence analysis. The analyzed viruses belong to IPNV genotype 5 and have 11 mutations in their VP2 protein. This is the first report of IPN outbreaks in farmed Atlantic salmon genetically resistant to IPNV in Chile. Similar outbreaks were previously reported in Scotland and Norway during 2018 and 2019, respectively. This study highlights the importance of maintaining a comprehensive surveillance program in conjunction with the use of farmed Atlantic salmon genetically resistant to IPNV. Full article

(This article belongs to the Special Issue Virulence Mechanisms, Detection and Control of Aquatic Animal Viruses)

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