Pathogens

19 pages, 5491 KB

Open AccessEditor’s ChoiceArticle

Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294

by Pablo Winzer, Nicoleta Anghel, Dennis Imhof, Vreni Balmer, Luis-Miguel Ortega-Mora, Kayode K. Ojo, Wesley C. Van Voorhis, Joachim Müller and Andrew Hemphill

Pathogens 2020, 9(5), 382; https://doi.org/10.3390/pathogens9050382 - 16 May 2020

Cited by 19 | Viewed by 3775

Abstract

Background: Bumped kinase inhibitors (BKIs) are potential drugs for neosporosis treatment in farm animals. BKI-1294 exposure results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs, the re-emergence [...] Read more.

Background: Bumped kinase inhibitors (BKIs) are potential drugs for neosporosis treatment in farm animals. BKI-1294 exposure results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs, the re-emergence of viable tachyzoites following drug removal, and the localization of CDPK1, the molecular target of BKIs. Methods: N. caninum tachyzoites and MNCs were studied by TEM and immunofluorescence using antibodies directed against CDPK1, and against NcSAG1 and IMC1 as markers for tachyzoites and newly formed zoites, respectively. Results: After six days of drug exposure, MNCs lacked SAG1 surface expression but remained intracellular, and formed numerous zoites incapable of disjoining from each other. Following drug removal, proliferation continued, and zoites lacking NcSAG1 emerged from the periphery of these complexes, forming infective tachyzoites after 10 days. In intracellular tachyzoites, CDPK1 was evenly distributed but shifted towards the apical part once parasites were extracellular. This shift was not affected by BKI-1294. Conclusions: CDPK1 has a dynamic distribution depending on whether parasites are located within a host cell or outside. During MNC-to-tachyzoite reconversion newly formed tachyzoites are generated directly from MNCs through zoites of unknown surface antigen composition. Further in vivo studies are needed to determine if MNCs could lead to a persistent reservoir of infection after BKI treatment. Full article

(This article belongs to the Special Issue Neospora Caninum: Infection and Immunity)

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16 pages, 1016 KB

Open AccessEditor’s ChoiceArticle

Leptospira Survey in Wild Boar (Sus scrofa) Hunted in Tuscany, Central Italy

by Giovanni Cilia, Fabrizio Bertelloni, Marta Angelini, Domenico Cerri and Filippo Fratini

Pathogens 2020, 9(5), 377; https://doi.org/10.3390/pathogens9050377 - 14 May 2020

Cited by 28 | Viewed by 4379

Abstract

Leptospirosis is a re-emerging, worldwide zoonosis, and wild boar (Sus scrofa) are involved in its epidemiology as the reservoir. The aim of this study was to investigate the prevalence of Leptospira with serological, bacteriological, and molecular assays in wild boar hunted [...] Read more.

Leptospirosis is a re-emerging, worldwide zoonosis, and wild boar (Sus scrofa) are involved in its epidemiology as the reservoir. The aim of this study was to investigate the prevalence of Leptospira with serological, bacteriological, and molecular assays in wild boar hunted in Tuscany (Italy) during two hunting seasons. In total, 287 specimens of sera, kidneys, and liver were collected to perform microscopic agglutination tests (MATs), isolation, and RealTime PCR to detect pathogenic (lipL32 gene), intermediate (16S rRNA gene), and saprophytic (23S rRNA gene) Leptospira. Within sera, 39 (13.59%) were positive to the MAT, and Australis was the most represented serogroup (4.88%), followed by Pomona (4.18%), and Tarassovi (3.14%). Moreover, four Leptospira cultures were positive, and once isolates were identified, one was identified as L. borgpetersenii serovar Tarassovi, and three as L. interrogans serovar Bratislava. Pathogenic Leptospira DNA were detected in 32 wild boar kidneys (11.15%). The characterization through the amplification of the rrs2 gene highlighted their belonging to L. interrogans (23 kidneys), L. borgpetersenii (four), and L. kirschneri (one), while nine kidneys (3.14%) were positive for intermediate Leptospira, all belonging to L. fainei. The results of this study confirmed the importance of wild boar in the epidemiology of leptospirosis among wildlife in Central Italy. Full article

(This article belongs to the Special Issue Leptospira infections in Domestic and Wild Animal)

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17 pages, 7667 KB

Open AccessEditor’s ChoiceArticle

Identification of Transmission Routes of Campylobacter and On-Farm Measures to Reduce Campylobacter in Chicken

by Sara Frosth, Oskar Karlsson-Lindsjö, Adnan Niazi, Lise-Lotte Fernström and Ingrid Hansson

Pathogens 2020, 9(5), 363; https://doi.org/10.3390/pathogens9050363 - 9 May 2020

Cited by 32 | Viewed by 5530

Abstract

An in-depth analysis was performed on Swedish broiler producers that had delivered chickens with Campylobacter to slaughter over several years, in order to identify possible transmission routes and formulate effective measures to prevent chickens being colonized with Campylobacter. Between 2017 and 2019, 626 [...] Read more.

An in-depth analysis was performed on Swedish broiler producers that had delivered chickens with Campylobacter to slaughter over several years, in order to identify possible transmission routes and formulate effective measures to prevent chickens being colonized with Campylobacter. Between 2017 and 2019, 626 samples were collected at farm level and Campylobacter was isolated from 133 (21.2%). All C. jejuni and C. coli isolated from these samples were whole-genome sequenced, together with isolates from the corresponding cecum samples at slaughter (n = 256). Core genome multi-locus sequence typing (cgMLST) analysis, using schemes consisting of 1140 and 529 genes for C. jejuni and C. coli, respectively, revealed that nearby cattle, contaminated drinking water, water ponds, transport crates, and parent flocks were potential reservoirs of Campylobacter. A novel feature compared with previous studies is that measures were implemented and tested during the work. These contributed to a nationwide decrease in Campylobacter-positive flocks from 15.4% in 2016 to 4.6% in 2019, which is the lowest ever rate in Sweden. To conclude, there are different sources and routes of Campylobacter transmission to chickens from different broiler producers, and individual measures must be taken by each producer to prevent Campylobacter colonization of chickens. Full article

(This article belongs to the Special Issue Campylobacter Infections)

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15 pages, 5349 KB

Open AccessEditor’s ChoiceArticle

Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis

by Edyta B. Hendiger, Marcin Padzik, Ines Sifaoui, María Reyes-Batlle, Atteneri López-Arencibia, Aitor Rizo-Liendo, Carlos J. Bethencourt-Estrella, Desirée San Nicolás-Hernández, Olfa Chiboub, Rubén L. Rodríguez-Expósito, Marta Grodzik, Anna Pietruczuk-Padzik, Karolina Stępień, Gabriela Olędzka, Lidia Chomicz, José E. Piñero and Jacob Lorenzo-Morales

Pathogens 2020, 9(5), 350; https://doi.org/10.3390/pathogens9050350 - 5 May 2020

Cited by 29 | Viewed by 4781

Abstract

Free living, cosmopolitan amoebae from Acanthamoeba genus present a serious risk to human health. As facultative human parasites, these amoebae may cause Acanthamoeba keratitis (AK). Acanthamoeba keratitis is a severe, vision-threatening corneal infection with non-specific symptoms. The number of reported AK cases worldwide [...] Read more.

Free living, cosmopolitan amoebae from Acanthamoeba genus present a serious risk to human health. As facultative human parasites, these amoebae may cause Acanthamoeba keratitis (AK). Acanthamoeba keratitis is a severe, vision-threatening corneal infection with non-specific symptoms. The number of reported AK cases worldwide has been increasing every year. Moreover, 90% of Acanthamoeba keratitis cases are related to contact lens use. Wearing and storage contact lenses not in accordance with the physicians and manufacturers recommendations are the primary key risk factors of this disease. Amoebae can easily adhere to the contact lens surface and transmit to the corneal epithelium. Preventing amoebae adhesion to the contact lens surface could significantly decrease the number of AK infections. Until now, the effective therapy against AK is still under development. Currently proposed therapies are mainly limited to the chlorhexidine digluconate combined with propamidine isethionate or hexamidine applications, which are insufficient and very toxic to the eye. Due to lack of effective treatment, looking for new potential preventive agents is crucial to decrease the number of Acanthamoeba keratitis infections, especially among contact lens users. Nanoparticles have been already included in several novel therapies against bacteria, viruses, fungi, and protist. However, their anti-amoebic potential has not been fully tested yet. The aim of this study was to assess silver nanoparticles (AgNPs) and platinum nanoparticles (PtNPs) anti-amoebic activity and influence on the amoebae adhesion to the surface of four different groups of contact lenses—classified according to the Food and Drugs Administration (FDA) guidelines. The obtained results show that both tested nanoparticles were effective against Acanthamoeba trophozoites and decreased the amoebae adhesion to the contact lens surface. AgNPs showed better anti-amoebic activity to cytotoxicity dependence and reduced amoebae adhesion in a wider spectrum of the tested contact lenses. Our studies also confirmed that ionization next to hydration of the contact lens material is a crucial parameter influencing the Acanthamoeba adhesion to the contact lens surface. In conclusion, silver nanoparticles might be considered as a novel preventive agent against Acanthamoeba keratitis infection. Full article

(This article belongs to the Special Issue Selected Papers from the International Meeting on the Biology and Pathogenicity of Free-Living Amoebae (FLAM2019))

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13 pages, 1908 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Volatile Organic Compounds Obtained from Breath and Feces to Detect Mycobacterium tuberculosis Complex in Wild Boar (Sus scrofa) in Doñana National Park, Spain

by Pauline Nol, Radu Ionescu, Tesfalem Geremariam Welearegay, Jose Angel Barasona, Joaquin Vicente, Kelvin de Jesus Beleño-Sáenz, Irati Barrenetxea, Maria Jose Torres, Florina Ionescu and Jack Rhyan

Pathogens 2020, 9(5), 346; https://doi.org/10.3390/pathogens9050346 - 2 May 2020

Cited by 13 | Viewed by 3860

Abstract

The presence of Mycobacterium tuberculosis complex (MTBC) in wild swine, such as in wild boar (Sus scrofa) in Eurasia, is cause for serious concern. Development of accurate, efficient, and noninvasive methods to detect MTBC in wild swine would be highly beneficial [...] Read more.

The presence of Mycobacterium tuberculosis complex (MTBC) in wild swine, such as in wild boar (Sus scrofa) in Eurasia, is cause for serious concern. Development of accurate, efficient, and noninvasive methods to detect MTBC in wild swine would be highly beneficial to surveillance and disease management efforts in affected populations. Here, we describe the first report of identification of volatile organic compounds (VOC) obtained from the breath and feces of wild boar to distinguish between MTBC-positive and MTBC-negative boar. We analyzed breath and fecal VOC collected from 15 MTBC-positive and 18 MTBC-negative wild boar in Donaña National Park in Southeast Spain. Analyses were divided into three age classes, namely, adults (>2 years), sub-adults (12–24 months), and juveniles (<12 months). We identified significant compounds by applying the two-tailed statistical t-test for two samples assuming unequal variance, with an α value of 0.05. One statistically significant VOC was identified in breath samples from adult wild boar and 14 were identified in breath samples from juvenile wild boar. One statistically significant VOC was identified in fecal samples collected from sub-adult wild boar and three were identified in fecal samples from juvenile wild boar. In addition, discriminant function analysis (DFA) was used to build classification models for MTBC prediction in juvenile animals. Using DFA, we were able to distinguish between MTBC-positive juvenile wild boar and MTBC-negative juvenile wild boar using breath VOC or fecal VOC. Based on our results, further research is warranted and should be performed using larger sample sizes, as well as wild boar from various geographic locations, to verify these compounds as biomarkers for MTBC infection in this species. This new approach to detect MTBC infection in free-ranging wild boar potentially comprises a reliable and efficient screening tool for surveillance in animal populations. Full article

(This article belongs to the Special Issue Tuberculosis Epidemiology and Control in Multi-Host Systems)

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21 pages, 3014 KB

Open AccessEditor’s ChoiceReview

Pathogenomics and Management of Fusarium Diseases in Plants

by Sephra N. Rampersad

Pathogens 2020, 9(5), 340; https://doi.org/10.3390/pathogens9050340 - 1 May 2020

Cited by 100 | Viewed by 9658

Abstract

There is an urgency to supplant the heavy reliance on chemical control of Fusarium diseases in different economically important, staple food crops due to development of resistance in the pathogen population, the high cost of production to the risk-averse grower, and the concomitant [...] Read more.

There is an urgency to supplant the heavy reliance on chemical control of Fusarium diseases in different economically important, staple food crops due to development of resistance in the pathogen population, the high cost of production to the risk-averse grower, and the concomitant environmental impacts. Pathogenomics has enabled (i) the creation of genetic inventories which identify those putative genes, regulators, and effectors that are associated with virulence, pathogenicity, and primary and secondary metabolism; (ii) comparison of such genes among related pathogens; (iii) identification of potential genetic targets for chemical control; and (iv) better characterization of the complex dynamics of host–microbe interactions that lead to disease. This type of genomic data serves to inform host-induced gene silencing (HIGS) technology for targeted disruption of transcription of select genes for the control of Fusarium diseases. This review discusses the various repositories and browser access points for comparison of genomic data, the strategies for identification and selection of pathogenicity- and virulence-associated genes and effectors in different Fusarium species, HIGS and successful Fusarium disease control trials with a consideration of loss of RNAi, off-target effects, and future challenges in applying HIGS for management of Fusarium diseases. Full article

(This article belongs to the Special Issue Fusarium: Pathogenomics and Inherent Resistance)

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14 pages, 715 KB

Open AccessEditor’s ChoiceReview

Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

by Francesca Marino-Merlo, Emanuela Balestrieri, Claudia Matteucci, Antonio Mastino, Sandro Grelli and Beatrice Macchi

Pathogens 2020, 9(5), 342; https://doi.org/10.3390/pathogens9050342 - 1 May 2020

Cited by 33 | Viewed by 6233

Abstract

The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous [...] Read more.

The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous features of the diseases caused by HTLV-1, a common topic concerning related therapeutic treatments relies on the use of antiretrovirals. This review will compare the different approaches and opinions in this matter, giving a concise overview of preclinical as well as clinical studies covering all the aspects of antiretrovirals in HTLV-1 infection. Studies will be grouped on the basis of the class of antiretroviral, putting together both pre-clinical and clinical results and generally following a chronological order. Analysis of the existing literature highlights that a number of preclinical studies clearly demonstrate that different classes of antiretrovirals, already utilized as anti-HIV agents, are actually capable to efficiently contrast HTLV-1 infection. Nevertheless, the results of most of the clinical studies are generally discouraging on the same point. In conclusion, the design of new antiretrovirals more specifically focused on HTLV-1 targets, and/or the establishment of early treatments with antiretrovirals could hopefully change the perspectives of diseases caused by HTLV-1. Full article

(This article belongs to the Special Issue HTLV-1 Disease)

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16 pages, 4062 KB

Open AccessEditor’s ChoiceArticle

Genetic Diversity and Sequence Polymorphism of Two Genes Encoding Theileria parva Antigens Recognized by CD8⁺ T Cells among Vaccinated and Unvaccinated Cattle in Malawi

by Elisha Chatanga, Kyoko Hayashida, Walter Muleya, Kodai Kusakisako, Mohamed Abdallah Mohamed Moustafa, Bashir Salim, Ken Katakura, Chihiro Sugimoto, Nariaki Nonaka and Ryo Nakao

Pathogens 2020, 9(5), 334; https://doi.org/10.3390/pathogens9050334 - 30 Apr 2020

Cited by 12 | Viewed by 4244

Abstract

East Coast fever (ECF) is an acute fatal tick-borne disease of cattle caused by Theileria parva. It causes major losses in exotic and crossbreed cattle, but this could be prevented by a vaccine of T. parva if the vaccine is selected properly [...] Read more.

East Coast fever (ECF) is an acute fatal tick-borne disease of cattle caused by Theileria parva. It causes major losses in exotic and crossbreed cattle, but this could be prevented by a vaccine of T. parva if the vaccine is selected properly based on information from molecular epidemiology studies. The Muguga cocktail (MC) vaccine (Muguga, Kiambu 5 and Serengeti-transformed strains) has been used on exotic and crossbreed cattle. A total of 254 T. parva samples from vaccinated and unvaccinated cattle were used to understand the genetic diversity of T. parva in Malawi using partial sequences of the Tp1 and Tp2 genes encoding T. parva CD8⁺ antigens, known to be immunodominant and current candidate antigens for a subunit vaccine. Single nucleotide polymorphisms were observed at 14 positions (3.65%) in Tp1 and 156 positions (33.12%) in Tp2, plus short deletions in Tp1, resulting in 6 and 10 amino acid variants in the Tp1 and Tp2 genes, respectively. Most sequences were either identical or similar to T. parva Muguga and Kiambu 5 strains. This may suggest the possible expansion of vaccine components into unvaccinated cattle, or that a very similar genotype already existed in Malawi. This study provides information that support the use of MC to control ECF in Malawi. Full article

(This article belongs to the Section Animal Pathogens)

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17 pages, 1377 KB

Open AccessEditor’s ChoiceArticle

Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System

by Helena Lindgren, Kjell Eneslätt, Igor Golovliov, Carl Gelhaus, Patrik Rydén, Terry Wu and Anders Sjöstedt

Pathogens 2020, 9(5), 338; https://doi.org/10.3390/pathogens9050338 - 30 Apr 2020

Cited by 9 | Viewed by 2806

Abstract

Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. [...] Read more.

Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. The immune responses were characterized by use of splenocytes from naïve or Live vaccine strain- (LVS) or ∆clpB/∆wbtC-immunized Fischer 344 rats as effectors and bone marrow-derived macrophages infected with the highly virulent strain SCHU S4. A complex immune response was elicited, resulting in cytokine secretion, nitric oxide production, and efficient control of the intracellular bacterial growth. Addition of LVS-immune splenocytes elicited a significantly better control of bacterial growth than ∆clpB/∆wbtC splenocytes. This mirrored the efficacy of the vaccine candidates in the rat model. Lower levels of IFN-γ, TNF, fractalkine, IL-2, and nitrite were present in the co-cultures with ∆clpB/∆wbtC splenocytes than in those with splenocytes from LVS-immunized rats. Nitric oxide was found to be a correlate of protection, since the levels inversely correlated to the degree of protection and inhibition of nitric oxide production completely reversed the growth inhibition of SCHU S4. Overall, the results demonstrate that the co-culture assay with rat-derived cells is a suitable model to identify correlates of protection against highly virulent strains of F. tularensis Full article

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13 pages, 2502 KB

Open AccessEditor’s ChoiceArticle

The Role of the Maridi Dam in Causing an Onchocerciasis-Associated Epilepsy Epidemic in Maridi, South Sudan: An Epidemiological, Sociological, and Entomological Study

by T. L. Lakwo, S. Raimon, M. Tionga, J. N. Siewe Fodjo, P. Alinda, W. J. Sebit, J. Y. Carter and R. Colebunders

Pathogens 2020, 9(4), 315; https://doi.org/10.3390/pathogens9040315 - 24 Apr 2020

Cited by 43 | Viewed by 5882

Abstract

Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited [...] Read more.

Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited in November 2019 to conduct focus group discussions with village elders and assess the OV16 seroprevalence in 3- to 9-year-old children. Entomological assessments to map blackfly breeding sites and determine biting rates around the Maridi River were conducted. Historical data regarding various activities at the Maridi dam were obtained from the administrative authorities. Results: The Maridi dam was constructed in 1954–1955. Village elders reported an increasing number of children developing epilepsy, including nodding syndrome, from the early 1990s. Kazana 2 (the village closest to the dam; epilepsy prevalence 11.9%) had the highest OV16 seroprevalence: 40.0% among children 3–6 years old and 66.7% among children 7–9 years old. The Maridi dam spillway was found to be the only Simulium damnosum breeding site along the river, with biting rates reaching 202 flies/man/h. Conclusion: Onchocerciasis transmission rates are high in Maridi. Suitable breeding conditions at the Maridi dam, coupled with suboptimal onchocerciasis control measures, have probably played a major role in causing an epilepsy (including nodding syndrome) epidemic in the Maridi area. Full article

(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)

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17 pages, 3831 KB

Open AccessEditor’s ChoiceArticle

Venereal Transmission of Vesicular Stomatitis Virus by Culicoides sonorensis Midges

by Paula Rozo-Lopez, Berlin Londono-Renteria and Barbara S. Drolet

Pathogens 2020, 9(4), 316; https://doi.org/10.3390/pathogens9040316 - 24 Apr 2020

Cited by 22 | Viewed by 8515

Abstract

Culicoides sonorensis biting midges are well-known agricultural pests and transmission vectors of arboviruses such as vesicular stomatitis virus (VSV). The epidemiology of VSV is complex and encompasses a broad range of vertebrate hosts, multiple routes of transmission, and diverse vector species. In temperate [...] Read more.

Culicoides sonorensis biting midges are well-known agricultural pests and transmission vectors of arboviruses such as vesicular stomatitis virus (VSV). The epidemiology of VSV is complex and encompasses a broad range of vertebrate hosts, multiple routes of transmission, and diverse vector species. In temperate regions, viruses can overwinter in the absence of infected animals through unknown mechanisms, to reoccur the next year. Non-conventional routes for VSV vector transmission may help explain viral maintenance in midge populations during inter-epidemic periods and times of adverse conditions for bite transmission. In this study, we examined whether VSV could be transmitted venereally between male and female midges. Our results showed that VSV-infected females could venereally transmit virus to uninfected naïve males at a rate as high as 76.3% (RT-qPCR), 31.6% (virus isolation) during the third gonotrophic cycle. Additionally, VSV-infected males could venereally transmit virus to uninfected naïve females at a rate as high as 76.6% (RT-qPCR), 49.2% (virus isolation). Immunofluorescent staining of micro-dissected reproductive organs, immunochemical staining of midge histological sections, examination of internal reproductive organ morphology, and observations of mating behaviors were used to determine relevant anatomical sites for virus location and to hypothesize the potential mechanism for VSV transmission in C. sonorensis midges through copulation. Full article

(This article belongs to the Special Issue Untargeted Alternative Routes of Arbovirus Transmission)

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26 pages, 4754 KB

Open AccessEditor’s ChoiceReview

Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically

by Handi Dahmana and Oleg Mediannikov

Pathogens 2020, 9(4), 310; https://doi.org/10.3390/pathogens9040310 - 23 Apr 2020

Cited by 127 | Viewed by 24779

Abstract

Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such [...] Read more.

Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance. Full article

(This article belongs to the Special Issue Translational Research for Zoonotic Parasites: New Findings toward Improved Diagnostics, Therapy and Prevention)

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9 pages, 1207 KB

Open AccessEditor’s ChoiceArticle

Long-Term Incubation PrP^CWD with Soils Affects Prion Recovery but Not Infectivity

by Alsu Kuznetsova, Debbie McKenzie, Catherine Cullingham and Judd M. Aiken

Pathogens 2020, 9(4), 311; https://doi.org/10.3390/pathogens9040311 - 23 Apr 2020

Cited by 28 | Viewed by 5020

Abstract

Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate [...] Read more.

Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate that long-term incubation of CWD prions (generated from tg-mice infected with deer or elk prions) with illite, montmorillonite (Mte) and whole soils results in decreased recovery of PrP^CWD, suggesting that binding becomes more avid and irreversible with time. This continual decline of immunoblot PrP^CWD detection did not correlate with prion infectivity levels. Bioassay showed no significant differences in incubation periods between mice inoculated with 1% CWD brain homogenate (BH) and with the CWD-BH pre-incubated with quartz or Luvisolic Ae horizon for 1 or 30 weeks. After 55 weeks incubation with Chernozem and Luvisol, bound PrP^CWD was not detectable by immunoblotting but remained infectious. This study shows that although recovery of PrP^CWD bound to soil minerals and whole soils with time become more difficult, prion infectivity is not significantly altered. Detection of prions in soil is, therefore, not only affected by soil type but also by length of time of the prion–soil interaction. Full article

(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)

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25 pages, 2278 KB

Open AccessEditor’s ChoiceReview

Phenylpropanoid Pathway Engineering: An Emerging Approach towards Plant Defense

by Vivek Yadav, Zhongyuan Wang, Chunhua Wei, Aduragbemi Amo, Bilal Ahmed, Xiaozhen Yang and Xian Zhang

Pathogens 2020, 9(4), 312; https://doi.org/10.3390/pathogens9040312 - 23 Apr 2020

Cited by 356 | Viewed by 20245

Abstract

Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to [...] Read more.

Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to cell wall breaches by pathogens. The whole metabolomic pathway is a complex network regulated by multiple gene families and it exhibits refined regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. The pathway genes are involved in the production of anti-microbial compounds as well as signaling molecules. The engineering in the metabolic pathway has led to a new plant defense system of which various mechanisms have been proposed including salicylic acid and antimicrobial mediated compounds. In recent years, some key players like phenylalanine ammonia lyases (PALs) from the phenylpropanoid pathway are proposed to have broad spectrum disease resistance (BSR) without yield penalties. Now we have more evidence than ever, yet little understanding about the pathway-based genes that orchestrate rapid, coordinated induction of phenylpropanoid defenses in response to microbial attack. It is not astonishing that mutants of pathway regulator genes can show conflicting results. Therefore, precise engineering of the pathway is an interesting strategy to aim at profitably tailored plants. Here, this review portrays the current progress and challenges for phenylpropanoid pathway-based resistance from the current prospective to provide a deeper understanding. Full article

(This article belongs to the Special Issue Genomics, Molecular, Genetics, and Diversity of Plant Disease Resistance)

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13 pages, 866 KB

Open AccessEditor’s ChoiceReview

Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19)

by Muhammad Shahid Nadeem, Mazin A. Zamzami, Hani Choudhry, Bibi Nazia Murtaza, Imran Kazmi, Habib Ahmad and Abdul Rauf Shakoori

Pathogens 2020, 9(4), 307; https://doi.org/10.3390/pathogens9040307 - 22 Apr 2020

Cited by 67 | Viewed by 18636

Abstract

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a [...] Read more.

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions. Full article

(This article belongs to the Section Human Pathogens)

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14 pages, 905 KB

Open AccessEditor’s ChoiceReview

Effects of Mycoplasmas on the Host Cell Signaling Pathways

by Sergei N. Borchsenius, Innokentii E. Vishnyakov, Olga A. Chernova, Vladislav M. Chernov and Nikolai A. Barlev

Pathogens 2020, 9(4), 308; https://doi.org/10.3390/pathogens9040308 - 22 Apr 2020

Cited by 21 | Viewed by 7467

Abstract

Mycoplasmas are the smallest free-living organisms. Reduced sizes of their genomes put constraints on the ability of these bacteria to live autonomously and make them highly dependent on the nutrients produced by host cells. Importantly, at the organism level, mycoplasmal infections may cause [...] Read more.

Mycoplasmas are the smallest free-living organisms. Reduced sizes of their genomes put constraints on the ability of these bacteria to live autonomously and make them highly dependent on the nutrients produced by host cells. Importantly, at the organism level, mycoplasmal infections may cause pathological changes to the host, including cancer and severe immunological reactions. At the molecular level, mycoplasmas often activate the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) inflammatory response and concomitantly inhibit the p53-mediated response, which normally triggers the cell cycle and apoptosis. Thus, mycoplasmal infections may be considered as cancer-associated factors. At the same time, mycoplasmas through their membrane lipoproteins (LAMPs) along with lipoprotein derivatives (lipopeptide MALP-2, macrophage-activating lipopeptide-2) are able to modulate anti-inflammatory responses via nuclear translocation and activation of Nrf2 (the nuclear factor-E2-related anti-inflammatory transcription factor 2). Thus, interactions between mycoplasmas and host cells are multifaceted and depend on the cellular context. In this review, we summarize the current information on the role of mycoplasmas in affecting the host’s intracellular signaling mediated by the interactions between transcriptional factors p53, Nrf2, and NF-κB. A better understanding of the mechanisms underlying pathologic processes associated with reprogramming eukaryotic cells that arise during the mycoplasma-host cell interaction should facilitate the development of new therapeutic approaches to treat oncogenic and inflammatory processes. Full article

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

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12 pages, 409 KB

Open AccessEditor’s ChoiceArticle

Prevention and Control of Legionella and Pseudomonas spp. Colonization in Dental Units

by Benedetta Tuvo, Michele Totaro, Maria Luisa Cristina, Anna Maria Spagnolo, David Di Cave, Sara Profeti, Angelo Baggiani, Gaetano Privitera and Beatrice Casini

Pathogens 2020, 9(4), 305; https://doi.org/10.3390/pathogens9040305 - 21 Apr 2020

Cited by 32 | Viewed by 4774

Abstract

Introduction: Dental Unit Waterlines (DUWLs) have shown to be a source of Legionella infection. We report the experience of different dental healthcare settings where a risk management plan was implemented. Materials and methods: In a Hospital Odontostomatology Clinic (HOC) and three Private Dental [...] Read more.

Introduction: Dental Unit Waterlines (DUWLs) have shown to be a source of Legionella infection. We report the experience of different dental healthcare settings where a risk management plan was implemented. Materials and methods: In a Hospital Odontostomatology Clinic (HOC) and three Private Dental Clinics (PDCs) housing 13 and six dental units (DUs), respectively, an assessment checklist was applied to evaluate staff compliance with guideline recommendations. DUWLs microbial parameters were investigated before and after the application of corrective actions. Results: In the HOC a poor adherence to good practices was demonstrated, whereas protocols were carefully applied in PDCs. L. pneumophila sg 2–15 was isolated in 31% (4/13) and 33% (2/6) of DUs in HOC and PDCs, respectively, mainly from handpieces (32%, 6/19) with counts >10² colony-forming units per milliliter (CFU/L), often associated with P. aeruginosa (68%, 13/19). The shock disinfection with 3% v/v hydrogen peroxide (HP) showed a limited effect, with a recolonization period of about 4 weeks. Legionella was eradicated only after 6% v/v HP shock disinfection and filters-installation, whilst P. aeruginosa after the third shock disinfection with a solution of 4% v/v HP and biodegradable surfactants. Conclusions: Our data demonstrate the presence and persistence of microbial contamination within the DUWLs, which required strict adherence to control measures and the choice of effective disinfectants. Full article

(This article belongs to the Special Issue Legionella Contamination in Water Environment)

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16 pages, 2093 KB

Open AccessEditor’s ChoiceArticle

Molecular Characterization and Antimicrobial Susceptibility of C. jejuni Isolates from Italian Wild Bird Populations

by Francesca Marotta, Anna Janowicz, Lisa Di Marcantonio, Claudia Ercole, Guido Di Donato, Giuliano Garofolo and Elisabetta Di Giannatale

Pathogens 2020, 9(4), 304; https://doi.org/10.3390/pathogens9040304 - 20 Apr 2020

Cited by 16 | Viewed by 4013

Abstract

Poultry is considered a major reservoir of human campylobacteriosis. It also been reported that not only poultry, but also wild birds, are capable of carrying C. jejuni, thus demonstrating to be a risk of spreading the bacteria in the environment. To gain [...] Read more.

Poultry is considered a major reservoir of human campylobacteriosis. It also been reported that not only poultry, but also wild birds, are capable of carrying C. jejuni, thus demonstrating to be a risk of spreading the bacteria in the environment. To gain insight into the population structure and investigate the antimicrobial resistance genotypes and phenotypes, we analyzed a collection of 135 C. jejuni from 15 species of wild birds in Italy. MLST revealed the presence of 41 sequence types (STs) and 13 clonal complexes (CCs). ST-179 complex and the generalist ST-45 complex were the most prevalent. Core genome MLST revealed that C. jejuni from ST-45 complex clustered according to the bird species, unlike the ST-179 complex which featured 3 different species in the same cluster. Overall we found a moderate prevalence of resistance to tetracycline (12.5%), ciprofloxacin and nalidixic acid (10%). The novel ST isolated from one pigeon showed resistance to all the antibiotics tested. The ST-179 complex (33.3%) was identified with significantly higher nalidixic acid resistance relative to other tested STs. Nine AMR genes (tet(O), cmeA, cmeB, cmeC, cmeR, aad, blaOXA-61, blaOXA-184 and erm(B)) and 23S rRNA and gyrA-associated point mutations were also described, indicating a concordance level between genotypic and phenotypic resistance of 23.3%, 23.4% and of 37.5% for streptomycin, tetracycline and quinolones/fluoroquinolones, respectively. We recommend that particular attention should be given to wild birds as key sentinel animals for the ecosystem contamination surveillance. Full article

(This article belongs to the Special Issue Campylobacter Infections)

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20 pages, 1295 KB

Open AccessEditor’s ChoiceReview

Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins

by Irene Lo Cigno, Federica Calati, Silvia Albertini and Marisa Gariglio

Pathogens 2020, 9(4), 292; https://doi.org/10.3390/pathogens9040292 - 17 Apr 2020

Cited by 50 | Viewed by 8425

Abstract

The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition [...] Read more.

The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition reactivates the host innate immune response, reversing what until then was an unresponsive cellular state suitable for viral persistence and tumorigenesis. Given that the disruption of distinct mechanisms of immune evasion is an attractive strategy for cancer therapy, the race is on to gain a better understanding of E6/E7-induced immune escape and cancer progression. Here, we review recent literature on the interplay between E6/E7 and the innate immune signaling pathways cGAS/STING/TBK1, RIG-I/MAVS/TBK1, and Toll-like receptors (TLRs). The overall emerging picture is that E6 and E7 have evolved broad-spectrum mechanisms allowing for the simultaneous depletion of multiple rather than single innate immunity effectors. The cGAS/STING/TBK1 pathway appears to be the most heavily impacted, whereas the RIG-I/MAVS/TBK1, still partially functional in HPV-transformed cells, can be activated by the powerful RIG-I agonist M8, triggering the massive production of type I and III interferons (IFNs), which potentiates chemotherapy-mediated cell killing. Overall, the identification of novel therapeutic targets to restore the innate immune response in HPV-transformed cells could transform the way HPV-associated cancers are treated. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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13 pages, 1620 KB

Open AccessEditor’s ChoiceArticle

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

by Mohamed A. El-Mokhtar, Essam R. Othman, Maha Y. Khashbah, Ali Ismael, Mohamed AA Ghaliony, Mohamed Ismail Seddik and Ibrahim M. Sayed

Pathogens 2020, 9(4), 295; https://doi.org/10.3390/pathogens9040295 - 17 Apr 2020

Cited by 32 | Viewed by 3911

Abstract

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found [...] Read more.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission. Full article

(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)

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11 pages, 1018 KB

Open AccessEditor’s ChoiceReview

Novel Coronavirus: Current Understanding of Clinical Features, Diagnosis, Pathogenesis, and Treatment Options

by Mohammad Ridwane Mungroo, Naveed Ahmed Khan and Ruqaiyyah Siddiqui

Pathogens 2020, 9(4), 297; https://doi.org/10.3390/pathogens9040297 - 17 Apr 2020

Cited by 44 | Viewed by 10140

Abstract

Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family [...] Read more.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family to affect humans. Symptoms of COVID-19 include fever (88%), cough (68%), vomiting (5%) and diarrhoea (3.7%), and transmission of SARS-CoV-2 is thought to occur from human to human via respiratory secretions released by the infected individuals when coughing and sneezing. COVID-19 can be detected through computed tomography scans and confirmed through molecular diagnostics tools such as polymerase chain reaction. Currently, there are no effective treatments against SARS-CoV-2, hence antiviral drugs have been used to reduce the development of respiratory complications by reducing viral load. The purpose of this review is to provide a comprehensive update on the pathogenesis, clinical aspects, diagnosis, challenges and treatment of SARS-CoV-2 infections. Full article

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12 pages, 248 KB

Open AccessEditor’s ChoiceReview

Updated Management Guidelines for Clostridioides difficile in Paediatrics

by Margherita Gnocchi, Martina Gagliardi, Pierpacifico Gismondi, Federica Gaiani, Gian Luigi de’ Angelis and Susanna Esposito

Pathogens 2020, 9(4), 291; https://doi.org/10.3390/pathogens9040291 - 16 Apr 2020

Cited by 22 | Viewed by 5250

Abstract

Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of [...] Read more.

Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile. Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Clostridioides difficile)

15 pages, 932 KB

Open AccessEditor’s ChoiceReview

The Role of Apoptin in Chicken Anemia Virus Replication

by Cynthia Feng, Yingke Liang and Jose G. Teodoro

Pathogens 2020, 9(4), 294; https://doi.org/10.3390/pathogens9040294 - 16 Apr 2020

Cited by 16 | Viewed by 5520

Abstract

Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is [...] Read more.

Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is a protein of interest in anti-tumor therapy. CAV apoptin is known to localize to different subcellular compartments in transformed and non-transformed cells, depending on the DNA damage response, and the phosphorylation of several identified threonine residues. In addition, apoptin interacts with molecular machinery such as the anaphase promoting complex/cyclosome (APC/C) to inhibit the cell cycle and induce arrest in G2/M phase. While these functions of apoptin contribute to the tumor-selective effect of the protein, they also provide an important fundamental framework to apoptin’s role in viral infection, pathogenesis, and propagation. Here, we reviewed how the regulation, localization, and functions of apoptin contribute to the viral life cycle and postulated its importance in efficient replication of CAV. A model of the molecular biology of infection is critical to informing our understanding of CAV and other related animal viruses that threaten the agricultural industry. Full article

(This article belongs to the Special Issue Chicken Anaemia Virus Infection)

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23 pages, 487 KB

Open AccessEditor’s ChoiceReview

Legionella pneumophila and Protozoan Hosts: Implications for the Control of Hospital and Potable Water Systems

by Muhammad Atif Nisar, Kirstin E. Ross, Melissa H. Brown, Richard Bentham and Harriet Whiley

Pathogens 2020, 9(4), 286; https://doi.org/10.3390/pathogens9040286 - 15 Apr 2020

Cited by 41 | Viewed by 6264

Abstract

Legionella pneumophila is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires’ disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This [...] Read more.

Legionella pneumophila is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires’ disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This review collates the literature describing interactions between L. pneumophila and protozoan hosts in hospital and municipal potable water distribution systems. The effectiveness of currently available water disinfection protocols to control L. pneumophila and its protozoan hosts is explored. The studies identified in this systematic literature review demonstrated the failure of common disinfection procedures to achieve long term elimination of L. pneumophila and protozoan hosts from potable water. It has been demonstrated that protozoan hosts facilitate the intracellular replication and packaging of viable L. pneumophila in infectious vesicles; whereas, cyst-forming protozoans provide protection from prolonged environmental stress. Disinfection procedures and protozoan hosts also facilitate biogenesis of viable but non-culturable (VBNC) L. pneumophila which have been shown to be highly resistant to many water disinfection protocols. In conclusion, a better understanding of L. pneumophila-protozoan interactions and the structure of complex microbial biofilms is required for the improved management of L. pneumophila and the prevention of LD. Full article

(This article belongs to the Special Issue Legionella Contamination in Water Environment)

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17 pages, 1185 KB

Open AccessFeature PaperEditor’s ChoiceReview

The Role of Long Noncoding RNAs in Human Papillomavirus-associated Pathogenesis

by Surendra Sharma and Karl Munger

Pathogens 2020, 9(4), 289; https://doi.org/10.3390/pathogens9040289 - 15 Apr 2020

Cited by 31 | Viewed by 7217

Abstract

Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack [...] Read more.

Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack intrinsic enzymatic activities and they function by binding to cellular regulatory molecules, thereby subverting normal cellular homeostasis. Much effort has focused on identifying protein targets of the E6 and E7 proteins, but it has been estimated that ~98% of the human transcriptome does not encode proteins. There is a growing interest in studying noncoding RNAs as biochemical targets and biological mediators of human papillomavirus (HPV) E6/E7 oncogenic activities. This review focuses on HPV E6/E7 targeting cellular long noncoding RNAs, a class of biologically versatile molecules that regulate almost every known biological process and how this may contribute to viral oncogenesis. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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16 pages, 2541 KB

Open AccessEditor’s ChoiceArticle

First Whole Genome Sequence of Anaplasma platys, an Obligate Intracellular Rickettsial Pathogen of Dogs

by Alejandro Llanes and Sreekumari Rajeev

Pathogens 2020, 9(4), 277; https://doi.org/10.3390/pathogens9040277 - 10 Apr 2020

Cited by 14 | Viewed by 5177

Abstract

We have assembled the first genome draft of Anaplasma platys, an obligate intracellular rickettsia, and the only known bacterial pathogen infecting canine platelets. A. platys is a not-yet-cultivated bacterium that causes infectious cyclic canine thrombocytopenia, a potentially fatal disease in dogs. Despite [...] Read more.

We have assembled the first genome draft of Anaplasma platys, an obligate intracellular rickettsia, and the only known bacterial pathogen infecting canine platelets. A. platys is a not-yet-cultivated bacterium that causes infectious cyclic canine thrombocytopenia, a potentially fatal disease in dogs. Despite its global distribution and veterinary relevance, no genome sequence has been published so far for this pathogen. Here, we used a strategy based on metagenome assembly to generate a draft of the A. platys genome using the blood of an infected dog. The assembled draft is similar to other Anaplasma genomes in size, gene content, and synteny. Notable differences are the apparent absence of rbfA, a gene encoding a 30S ribosome-binding factor acting as a cold-shock protein, as well as two genes involved in biotin metabolism. We also observed differences associated with expanded gene families, including those encoding outer membrane proteins, a type IV secretion system, ankyrin repeat-containing proteins, and proteins with predicted intrinsically disordered regions. Several of these families have members highly divergent in sequence, likely to be associated with survival and interactions within the host and the vector. The sequence of the A. platys genome can benefit future studies regarding invasion, survival, and pathogenesis of Anaplasma species, while paving the way for the better design of treatment and prevention strategies against these neglected intracellular pathogens. Full article

(This article belongs to the Section Animal Pathogens)

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13 pages, 1770 KB

Open AccessEditor’s ChoiceArticle

High-Resolution Melting (HRM) Curve Assay for the Identification of Eight Fusarium Species Causing Ear Rot in Maize

by Simon Schiwek, Lukas Beule, Maria Vinas, Annette Pfordt, Andreas von Tiedemann and Petr Karlovsky

Pathogens 2020, 9(4), 270; https://doi.org/10.3390/pathogens9040270 - 7 Apr 2020

Cited by 26 | Viewed by 5807

Abstract

Maize plants are often infected with fungal pathogens of the genus Fusarium. Taxonomic characterization of these species by microscopic examination of pure cultures or assignment to mating populations is time-consuming and requires specific expertise. Reliable taxonomic assignment may be strengthened by the [...] Read more.

Maize plants are often infected with fungal pathogens of the genus Fusarium. Taxonomic characterization of these species by microscopic examination of pure cultures or assignment to mating populations is time-consuming and requires specific expertise. Reliable taxonomic assignment may be strengthened by the analysis of DNA sequences. Species-specific PCR assays are available for most Fusarium pathogens, but the number of species that infect maize increases the labor and costs required for analysis. In this work, a diagnostic assay for major Fusarium pathogens of maize based on the analysis of melting curves of PCR amplicons was established. Short segments of genes RPB2 and TEF-1α, which have been widely used in molecular taxonomy of Fusarium, were amplified with universal primers in a real-time thermocycler and high-resolution melting (HRM) curves of the products were recorded. Among major Fusarium pathogens of maize ears, F. cerealis, F. culmorum, F. graminearum, F. equiseti, F. poae, F. temperatum, F. tricinctum, and F. verticillioides, all species except for the pair F. culmorum/F. graminearum could be distinguished by HRM analysis of a 304 bp segment of the RPB2 gene. The latter two species could be differentiated by HRM analysis of a 247 bp segment of the TEF-1α gene. The assay was validated with DNA extracted from pure cultures of fungal strains, successfully applied to total DNA extracted from infected maize ears and also to fungal mycelium that was added directly to the PCR master mix (“colony PCR”). HRM analysis thus offers a cost-efficient method suitable for the diagnosis of multiple fungal pathogens. Full article

(This article belongs to the Section Plant Pathogens)

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15 pages, 1281 KB

Open AccessEditor’s ChoiceReview

A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population

by Jacob Dag Berild, Brita Askeland Winje, Didrik Frimann Vestrheim, Hans-Christian Slotved, Palle Valentiner-Branth, Adam Roth and Jann Storsäter

Pathogens 2020, 9(4), 259; https://doi.org/10.3390/pathogens9040259 - 3 Apr 2020

Cited by 41 | Viewed by 6980

Abstract

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the [...] Read more.

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle–Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time. Full article

(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)

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28 pages, 1972 KB

Open AccessEditor’s ChoiceReview

The Neuropathic Itch Caused by Pseudorabies Virus

by Kathlyn Laval and Lynn W. Enquist

Pathogens 2020, 9(4), 254; https://doi.org/10.3390/pathogens9040254 - 31 Mar 2020

Cited by 76 | Viewed by 10972

Abstract

Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it [...] Read more.

Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it can establish a quiescent, latent infection. While the natural host of PRV is the swine, a broad spectrum of mammals, including rodents, cats, dogs, and cattle can be infected. Since the nineteenth century, PRV infection is known to cause a severe acute neuropathy, the so called “mad itch” in non-natural hosts, but surprisingly not in swine. In the past, most scientific efforts have been directed to eradicating PRV from pig farms by the use of effective marker vaccines, but little attention has been given to the processes leading to the mad itch. The main objective of this review is to provide state-of-the-art information on the mechanisms governing PRV-induced neuropathic itch in non-natural hosts. We highlight similarities and key differences in the pathogenesis of PRV infections between non-natural hosts and pigs that might explain their distinctive clinical outcomes. Current knowledge on the neurobiology and possible explanations for the unstoppable itch experienced by PRV-infected animals is also reviewed. We summarize recent findings concerning PRV-induced neuroinflammatory responses in mice and address the relevance of this animal model to study other alphaherpesvirus-induced neuropathies, such as those observed for VZV infection. Full article

(This article belongs to the Special Issue Pseudorabies Virus Infections)

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15 pages, 2222 KB

Open AccessEditor’s ChoiceArticle

Modeling of the HIV-1 Life Cycle in Productively Infected Cells to Predict Novel Therapeutic Targets

by Olga Shcherbatova, Dmitry Grebennikov, Igor Sazonov, Andreas Meyerhans and Gennady Bocharov

Pathogens 2020, 9(4), 255; https://doi.org/10.3390/pathogens9040255 - 31 Mar 2020

Cited by 26 | Viewed by 7840

Abstract

There are many studies that model the within-host population dynamics of Human Immunodeficiency Virus Type 1 (HIV-1) infection. However, the within-infected-cell replication of HIV-1 remains to be not comprehensively addressed. There exist rather few quantitative models describing the regulation of the HIV-1 life [...] Read more.

There are many studies that model the within-host population dynamics of Human Immunodeficiency Virus Type 1 (HIV-1) infection. However, the within-infected-cell replication of HIV-1 remains to be not comprehensively addressed. There exist rather few quantitative models describing the regulation of the HIV-1 life cycle at the intracellular level. In treatment of HIV-1 infection, there remain issues related to side-effects and drug-resistance that require further search “...for new and better drugs, ideally targeting multiple independent steps in the HIV-1 replication cycle” (as highlighted recently by Tedbury & Freed, The Future of HIV-1 Therapeutics, 2015). High-resolution mathematical models of HIV-1 growth in infected cells provide an additional analytical tool in identifying novel drug targets. We formulate a high-dimensional model describing the biochemical reactions underlying the replication of HIV-1 in target cells. The model considers a nonlinear regulation of the transcription of HIV-1 mediated by Tat and the Rev-dependent transport of fully spliced and singly spliced transcripts from the nucleus to the cytoplasm. The model is calibrated using available information on the kinetics of various stages of HIV-1 replication. The sensitivity analysis of the model is performed to rank the biochemical processes of HIV-1 replication with respect to their impact on the net production of virions by one actively infected cell. The ranking of the sensitivity factors provides a quantitative basis for identifying novel targets for antiviral therapy. Our analysis suggests that HIV-1 assembly depending on Gag and Tat-Rev regulation of transcription and mRNA distribution present two most critical stages in HIV-1 replication that can be targeted to effectively control virus production. These processes are not covered by current antiretroviral treatments. Full article

(This article belongs to the Special Issue Modeling Virus Dynamics and Evolution)

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12 pages, 1706 KB

Open AccessEditor’s ChoiceArticle

In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus

by Brianna Atto, Roger Latham, Dale Kunde, David A Gell and Stephen Tristram

Pathogens 2020, 9(4), 243; https://doi.org/10.3390/pathogens9040243 - 25 Mar 2020

Cited by 9 | Viewed by 3592

Abstract

Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a [...] Read more.

Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible individuals. Here, we assess the preliminary feasibility of this approach by direct in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. Subsequent changes in NTHi growth rate and fitness, in conjunction with HPL expression analysis, were employed to assess the NTHi-inhibitory capacity of Hh strains. HPL-producing strains of Hh not only outcompeted NTHi during short-term and extended co-culture, but also demonstrated a growth advantage compared with Hh strains unable to produce the protein. Additionally, HPL expression levels during competition correlated with the NTHi-inhibitory phenotype. HPL-producing strains of Hh demonstrate significant probiotic potential against NTHi colonization in the upper respiratory tract, however, further investigations are warranted to demonstrate a range of other characteristics that would support the eventual development of a probiotic. Full article

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12 pages, 2796 KB

Open AccessEditor’s ChoiceArticle

Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2

by Saif ur Rehman, Laiba Shafique, Awais Ihsan and Qingyou Liu

Pathogens 2020, 9(3), 240; https://doi.org/10.3390/pathogens9030240 - 23 Mar 2020

Cited by 168 | Viewed by 29198

Abstract

Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study [...] Read more.

Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study aimed to track the evolutionary ancestors and different evolutionary strategies that were genetically adapted by SARS-CoV-2. Our whole-genome analysis revealed that SARS-CoV-2 was the descendant of Bat SARS/SARS-like CoVs and bats served as a natural reservoir. SARS-CoV-2 used mutations and recombination as crucial strategies in different genomic regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time we identified nine putative recombination patterns in SARS-CoV-2, which encompass spike glycoprotein, RdRp, helicase and ORF3a. Six recombination regions were spotted in the S gene and are undoubtedly important for evolutionary survival, meanwhile this permitted the virus to modify superficial antigenicity to find a way from immune reconnaissance in animals and adapt to a human host. With these combined natural selected strategies, SARS-CoV-2 emerged as a novel virus in human society. Full article

(This article belongs to the Section Animal Pathogens)

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10 pages, 1130 KB

Open AccessEditor’s ChoiceArticle

Characterization of the Humoral Immune Response to Porcine Epidemic Diarrhea Virus Infection under Experimental and Field Conditions Using an AlphaLISA Platform

by Kay Kimpston-Burkgren, Juan Carlos Mora-Díaz, Philippe Roby, Jordan Bjustrom-Kraft, Rodger Main, Roger Bosse and Luis Gabriel Giménez-Lirola

Pathogens 2020, 9(3), 233; https://doi.org/10.3390/pathogens9030233 - 21 Mar 2020

Cited by 10 | Viewed by 4527

Abstract

Coronavirus infections are a continuous threat raised time and again. With the recent emergence of novel virulent strains, these viruses can have a large impact on human and animal health. Porcine epidemic diarrhea (PED) is considered to be a reemerging pig disease caused [...] Read more.

Coronavirus infections are a continuous threat raised time and again. With the recent emergence of novel virulent strains, these viruses can have a large impact on human and animal health. Porcine epidemic diarrhea (PED) is considered to be a reemerging pig disease caused by the enteropathogenic alphacoronavirus PED virus (PEDV). In the absence of effective vaccines, infection prevention and control through diagnostic testing and quarantine are critical. Early detection and differential diagnosis of PEDV infections increase the chance of successful control of the disease. Therefore, there is a continuous need for development of reduced assay-step protocols, no-wash, high-throughput immunoassays. This study described the characterization of the humoral immune response against PEDV under experimental and field conditions using a rapid, sensitive, luminescent proximity homogenous assay (AlphaLISA). PEDV IgG and IgA antibodies were developed toward the beginning of the second week of infection. PEDV IgG antibodies were detected for at least 16 weeks post-exposure. Remarkably, the serum IgA levels remained high and relatively stable throughout the study, lasting longer than the serum IgG response. Overall, AlphaLISA allows the detection and characterization of pathogen-specific antibodies with new speed, sensitivity, and simplicity of use. Particularly, the bridge assay constitutes a rapid diagnostic that substantially improves upon the “time to result” metric of currently available immunoassays. Full article

(This article belongs to the Special Issue Immune Response to Porcine Epidemic Diarrhea Virus)

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21 pages, 2582 KB

Open AccessEditor’s ChoiceReview

The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis

by Aude Cerutti, Nicolas Blanchard and Sébastien Besteiro

Pathogens 2020, 9(3), 234; https://doi.org/10.3390/pathogens9030234 - 21 Mar 2020

Cited by 79 | Viewed by 18552

Abstract

Toxoplasma gondii is a ubiquitous parasitic protist found in a wide variety of hosts, including a large proportion of the human population. Beyond an acute phase which is generally self-limited in immunocompetent individuals, the ability of the parasite to persist as a dormant [...] Read more.

Toxoplasma gondii is a ubiquitous parasitic protist found in a wide variety of hosts, including a large proportion of the human population. Beyond an acute phase which is generally self-limited in immunocompetent individuals, the ability of the parasite to persist as a dormant stage, called bradyzoite, is an important aspect of toxoplasmosis. Not only is this stage not eliminated by current treatments, but it can also reactivate in immunocompromised hosts, leading to a potentially fatal outcome. Yet, despite its critical role in the pathology, the bradyzoite stage is relatively understudied. One main explanation is that it is a considerably challenging model, which essentially has to be derived from in vivo sources. However, recent progress on genetic manipulation and in vitro differentiation models now offers interesting perspectives for tackling key biological questions related to this particularly important developmental stage. Full article

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17 pages, 1920 KB

Open AccessEditor’s ChoiceArticle

Impact of Environmental Conditions and Agronomic Practices on the Prevalence of Fusarium Species Associated with Ear- and Stalk Rot in Maize

by Annette Pfordt, Lucia Ramos Romero, Simon Schiwek, Petr Karlovsky and Andreas von Tiedemann

Pathogens 2020, 9(3), 236; https://doi.org/10.3390/pathogens9030236 - 21 Mar 2020

Cited by 74 | Viewed by 8403

Abstract

Fusarium species are common pathogens on maize and reduce the product quality through contamination with mycotoxins thus jeopardizing safety of both animal feed and human food products. Monitoring of Fusarium infected maize ears and stalks was conducted in Germany to determine the range [...] Read more.

Fusarium species are common pathogens on maize and reduce the product quality through contamination with mycotoxins thus jeopardizing safety of both animal feed and human food products. Monitoring of Fusarium infected maize ears and stalks was conducted in Germany to determine the range of Fusarium species present in the field and to assess the impact of tillage, crop rotation, and weather conditions on the frequency of Fusarium species. From 2016 till 2018, a total of 387 infected ears and 190 stalk segments from 58 locations in Germany were collected. For each sample location, site-specific agronomic data on tillage and previous crops as well as meteorological data on precipitation, air temperature, and relative humidity during the vegetation period were recorded. The most frequent Fusarium species detected in maize ears were Fusarium graminearum, F. verticillioides and F. temperatum, whereas, F. graminearum, F. equiseti, F. culmorum, and F. temperatum were the species prevailing on maize stalks. Differences in the local species composition were found to be primarily associated with weather variations between the years and the microclimate at the different locations. The results indicate that mean temperature and precipitation in July, during flowering, has the strongest impact on the local range of Fusarium spp. on ears, whereas the incidence of Fusarium species on stalks is mostly affected by weather conditions during September. Ploughing significantly reduced the infection with F. graminearum and F. temperatum, while crop rotation exerted only minor effects. Full article

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14 pages, 3323 KB

Open AccessEditor’s ChoiceReview

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

by Firas A. Rabi, Mazhar S. Al Zoubi, Ghena A. Kasasbeh, Dunia M. Salameh and Amjad D. Al-Nasser

Pathogens 2020, 9(3), 231; https://doi.org/10.3390/pathogens9030231 - 20 Mar 2020

Cited by 534 | Viewed by 146490

Abstract

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and [...] Read more.

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes. Full article

(This article belongs to the Collection SARS-CoV Infections)

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20 pages, 2856 KB

Open AccessEditor’s ChoiceArticle

Compost Amendments Based on Vinegar Residue Promote Tomato Growth and Suppress Bacterial Wilt Caused by Ralstonia Solanacearum

by Mingming He, Mohammad Shah Jahan, Yu Wang, Jin Sun, Sheng Shu and Shirong Guo

Pathogens 2020, 9(3), 227; https://doi.org/10.3390/pathogens9030227 - 19 Mar 2020

Cited by 31 | Viewed by 5941

Abstract

Tomato bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating soil-borne diseases, and compost is to be considered as a resource-saving and environment-friendly measure to control the disease. Herein, a pot experiment was implemented to explore the effects of [...] Read more.

Tomato bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating soil-borne diseases, and compost is to be considered as a resource-saving and environment-friendly measure to control the disease. Herein, a pot experiment was implemented to explore the effects of vinegar residue matrix amendments on the growth performances of tomato seedlings and to examine the suppression ability against bacterial wilt under vinegar residue substrate (VRS), and peat substrate (Peat) with RS inoculation. The results revealed that VRS effectively suppressed the disease incidence of bacterial wilt, increased the number of bacteria and actinomycetes, decreased fungi populations, promoted soil microbial populations and microbial activities, enhanced the growths of tomato seedlings, and modulated defense mechanism. In addition, VRS efficiently inhibited the oxidative damage in RS inoculated leaves via the regulation of excess reactive oxide species (O₂^•− and H₂O₂) production, lessening of malondialdehyde (MDA) content, and causing less membrane injury; resulting in enhancements of antioxidants enzymes activities accompanying with modulating their encoding gene expression. The transcription levels of NPR1, PIN2, PR1b, ACO1, EDS1, PR1B, MAPK3, PIN2, and RRS1 were also modulated with the pathogens inoculated in tomato leaves both in VRS and Peat treatments, which indicated that systemic-acquired resistance possesses cross-talk between salicylic acid, jasmonic acid, and the ethylene-dependent signaling pathway. Besides, the RS inoculation significantly inhibited the growth of tomato seedlings, and all growth indices of plants grown in VRS were considerably higher than those produced in Peat. Taken together, VRS represents a new strategy to control tomato bacterial wilt through boosting the soil microbial populations and microbial activities. Furthermore, VRS promotes the plant immune response to provide a better growth environment for plants surviving in disease conditions. Full article

(This article belongs to the Special Issue Control of Plant Pathogenic Bacteria with the Lowest Environmental Impact)

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14 pages, 4814 KB

Open AccessEditor’s ChoiceArticle

Free to Circulate: An Update on the Epidemiological Dynamics of Porcine Circovirus 2 (PCV-2) in Italy Reveals the Role of Local Spreading, Wild Populations, and Foreign Countries

by Giovanni Franzo, Susanna Tinello, Laura Grassi, Claudia Maria Tucciarone, Matteo Legnardi, Mattia Cecchinato, Giorgia Dotto, Alessandra Mondin, Marco Martini, Daniela Pasotto, Maria Luisa Menandro and Michele Drigo

Pathogens 2020, 9(3), 221; https://doi.org/10.3390/pathogens9030221 - 17 Mar 2020

Cited by 25 | Viewed by 4126

Abstract

Porcine circovirus 2 (PCV-2) is one of the most impactful and widespread pathogens of the modern swine industry. Unlike other DNA viruses, PCV-2 is featured by a remarkable genetic variability, which has led to the emergence and recognition of different genotypes, some of [...] Read more.

Porcine circovirus 2 (PCV-2) is one of the most impactful and widespread pathogens of the modern swine industry. Unlike other DNA viruses, PCV-2 is featured by a remarkable genetic variability, which has led to the emergence and recognition of different genotypes, some of which (PCV-2a, 2b, and 2d) have alternated over time. Currently, PCV-2d is considered the most prevalent genotype, and some evidence of differential virulence and vaccine efficacy have been reported. Despite the potential practical relevance, the data on PCV-2 epidemiology in Italy are quite outdated and do not quantify the actual circulation of this genotype in Italy. In the present study, 82 complete ORF2 sequences were obtained from domestic pigs and wild boars sampled in Northern Italy in the period 2013–2018 and merged with those previously obtained from Italy and other countries. A combination of phylogenetic, haplotype network, and phylodynamic analyses were used to genotype the collected strains and evaluate the temporal trend and the spatial and host spread dynamics. A rising number of PCV-2d detections was observed in domestic pigs, particularly since 2013, reaching a detection frequency comparable to PCV-2b. A similar picture was observed in wild boars, although a lower sequence number was available. Overall, the present study demonstrates the extreme complexity of PCV-2 molecular epidemiology in Italy, the significant spread across different regions, the recurrent introduction from foreign countries, and the frequent occurrence of recombination events. Although a higher viral flux occurred from domestic to wild populations than vice versa, wild boars seem to maintain PCV-2 infection and spread it over relatively long distances. Full article

(This article belongs to the Special Issue Porcine Circovirus Infections)

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18 pages, 323 KB

Open AccessEditor’s ChoiceReview

Immunotherapy against Prion Disease

by Yue Ma and Jiyan Ma

Pathogens 2020, 9(3), 216; https://doi.org/10.3390/pathogens9030216 - 14 Mar 2020

Cited by 23 | Viewed by 7191

Abstract

The term “prion disease” encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant [...] Read more.

The term “prion disease” encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant Creutzfeldt–Jakob disease in humans; (b) the heated debate about the prion hypothesis; and (c) the availability of a natural prion disease in rodents, the understanding of the pathogenic process in prion disease is much more advanced compared to that of other neurodegenerative disorders, which inspired many attempts to develop therapeutic strategies against these fatal diseases. In this review, we focus on immunotherapy against prion disease. We explain our rationale for immunotherapy as a plausible therapeutic choice, review previous trials using either active or passive immunization, and discuss potential strategies for overcoming the hurdles in developing a successful immunotherapy. We propose that immunotherapy is a plausible and practical therapeutic strategy and advocate more studies in this area to develop effective measures to control and treat these devastating disorders. Full article

(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)

24 pages, 4228 KB

Open AccessEditor’s ChoiceArticle

Viromes of Ten Alfalfa Plants in Australia Reveal Diverse Known Viruses and a Novel RNA Virus

by Samira Samarfard, Alistair R. McTaggart, Murray Sharman, Nicolás E. Bejerman and Ralf G. Dietzgen

Pathogens 2020, 9(3), 214; https://doi.org/10.3390/pathogens9030214 - 13 Mar 2020

Cited by 21 | Viewed by 6247

Abstract

Alfalfa plants in the field can display a range of virus-like symptoms, especially when grown over many years for seed production. Most known alfalfa viruses have RNA genomes, some of which can be detected using diagnostic assays, but many viruses of alfalfa are [...] Read more.

Alfalfa plants in the field can display a range of virus-like symptoms, especially when grown over many years for seed production. Most known alfalfa viruses have RNA genomes, some of which can be detected using diagnostic assays, but many viruses of alfalfa are not well characterized. This study aims to identify the RNA and DNA virus complexes associated with alfalfa plants in Australia. To maximize the detection of RNA viruses, we purified double-stranded RNA (dsRNA) for high throughput sequencing and characterized the viromes of ten alfalfa samples that showed diverse virus-like symptoms. Using Illumina sequencing of tagged cDNA libraries from immune-captured dsRNA, we identified sequences of the single-stranded RNA viruses, alfalfa mosaic virus (AMV), bean leafroll virus, a new emaravirus tentatively named alfalfa ringspot-associated virus, and persistent dsRNA viruses belonging to the families Amalgaviridae and Partitiviridae. Furthermore, rolling circle amplification and restriction enzyme digestion revealed the complete genome of chickpea chlorosis Australia virus, a mastrevirus (family Geminiviridae) previously reported only from chickpea and French bean that was 97% identical to the chickpea isolate. The sequence data also enabled the assembly of the first complete genome (RNAs 1–3) of an Australian AMV isolate from alfalfa. Full article

(This article belongs to the Section Plant Pathogens)

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21 pages, 2911 KB

Open AccessEditor’s ChoiceArticle

Rodents as Hosts of Pathogens and Related Zoonotic Disease Risk

by Handi Dahmana, Laurent Granjon, Christophe Diagne, Bernard Davoust, Florence Fenollar and Oleg Mediannikov

Pathogens 2020, 9(3), 202; https://doi.org/10.3390/pathogens9030202 - 10 Mar 2020

Cited by 101 | Viewed by 11719

Abstract

Rodents are known to be reservoir hosts for at least 60 zoonotic diseases and are known to play an important role in their transmission and spread in different ways. We sampled different rodent communities within and around human settlements in Northern Senegal, an [...] Read more.

Rodents are known to be reservoir hosts for at least 60 zoonotic diseases and are known to play an important role in their transmission and spread in different ways. We sampled different rodent communities within and around human settlements in Northern Senegal, an area subjected to major environmental transformations associated with global changes. Herein, we conducted an epidemiological study on their bacterial communities. One hundred and seventy-one (171) invasive and native rodents were captured, 50 from outdoor trapping sites and 121 rodents from indoor habitats, consisting of five species. The DNA of thirteen pathogens was successfully screened on the rodents’ spleens. We found: 2.3% of spleens positive to Piroplasmida and amplified one which gave a potentially new species Candidatus “Theileria senegalensis”; 9.35% of Bartonella spp. and amplified 10, giving three genotypes; 3.5% of filariasis species; 18.12% of Anaplasmataceae species and amplified only 5, giving a new potential species Candidatus “Ehrlichia senegalensis”; 2.33% of Hepatozoon spp.; 3.5% of Kinetoplastidae spp.; and 15.2% of Borrelia spp. and amplified 8 belonging all to Borrelia crocidurae. Some of the species of pathogens carried by the rodents of our studied area may be unknown because most of those we have identified are new species. In one bacterial taxon, Anaplasma, a positive correlation between host body mass and infection was found. Overall, male and invasive rodents appeared less infected than female and native ones, respectively. Full article

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21 pages, 292 KB

Open AccessEditor’s ChoiceReview

Animal Models of Lassa Fever

by Rachel A. Sattler, Slobodan Paessler, Hinh Ly and Cheng Huang

Pathogens 2020, 9(3), 197; https://doi.org/10.3390/pathogens9030197 - 6 Mar 2020

Cited by 35 | Viewed by 6202

Abstract

Lassa virus (LASV), the causative agent of Lassa fever, is estimated to be responsible for up to 300,000 new infections and 5000 deaths each year across Western Africa. The most recent 2018 and 2019 Nigerian outbreaks featured alarmingly high fatality rates of up [...] Read more.

Lassa virus (LASV), the causative agent of Lassa fever, is estimated to be responsible for up to 300,000 new infections and 5000 deaths each year across Western Africa. The most recent 2018 and 2019 Nigerian outbreaks featured alarmingly high fatality rates of up to 25.4%. In addition to the severity and high fatality of the disease, a significant population of survivors suffer from long-term sequelae, such as sensorineural hearing loss, resulting in a huge socioeconomic burden in endemic regions. There are no Food and Drug Administration (FDA)-approved vaccines, and therapeutics remain extremely limited for Lassa fever. Development of countermeasures depends on relevant animal models that can develop a disease strongly mimicking the pathogenic features of Lassa fever in humans. The objective of this review is to evaluate the currently available animal models for LASV infection with an emphasis on their pathogenic and histologic characteristics as well as recent advances in the development of a suitable rodent model. This information may facilitate the development of an improved animal model for understanding disease pathogenesis of Lassa fever and for vaccine or antiviral testing. Full article

(This article belongs to the Special Issue Lassa Fever: Viral Replication, Disease Pathogenesis, and Host Immune Modulations)

15 pages, 960 KB

Open AccessEditor’s ChoiceReview

Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks

by Hossam M. Ashour, Walid F. Elkhatib, Md. Masudur Rahman and Hatem A. Elshabrawy

Pathogens 2020, 9(3), 186; https://doi.org/10.3390/pathogens9030186 - 4 Mar 2020

Cited by 443 | Viewed by 58184

Abstract

Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in [...] Read more.

Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat. Full article

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16 pages, 320 KB

Open AccessEditor’s ChoiceArticle

Bartonella spp. Prevalence (Serology, Culture, and PCR) in Sanitary Workers in La Rioja Spain

by Aránzazu Portillo, Ricardo Maggi, José A. Oteo, Julie Bradley, Lara García-Álvarez, Montserrat San-Martín, Xavier Roura and Edward Breitschwerdt

Pathogens 2020, 9(3), 189; https://doi.org/10.3390/pathogens9030189 - 4 Mar 2020

Cited by 33 | Viewed by 5032

Abstract

Bartonella spp. are increasingly implicated in association with a spectrum of zoonotic infectious diseases. One hundred sanitary workers in La Rioja, Spain, completed a questionnaire and provided blood specimens for Bartonella spp. serology and Bartonella Alpha-Proteobacteria growth medium (BAPGM) enrichment blood culture/PCR. Six [...] Read more.

Bartonella spp. are increasingly implicated in association with a spectrum of zoonotic infectious diseases. One hundred sanitary workers in La Rioja, Spain, completed a questionnaire and provided blood specimens for Bartonella spp. serology and Bartonella Alpha-Proteobacteria growth medium (BAPGM) enrichment blood culture/PCR. Six immunofluorescence assays (IFA) were performed and aseptically obtained blood specimens were inoculated into liquid BAPGM and subcultured onto blood agar plates. Bartonella DNA was amplified using conventional and real-time PCR assays. The Bartonella spp., strain, or genotype was determined by DNA sequencing. Bartonella seroreactivity was documented in 83.1% and bloodstream infection in 21.6% of participants. Bartonella henselae, B. vinsonii subsp. berkhoffii genotypes I and III, and B. quintana were identified. IFA seroreactivity and PCR positivity were not statistically associated with self-reported symptoms. Our results suggest that exposure to and non-clinical infection with Bartonella spp. may occur more often than previously suspected in the La Rioja region. Full article

(This article belongs to the Section Human Pathogens)

13 pages, 1080 KB

Open AccessEditor’s ChoiceArticle

Development of a High-Throughput Serum Neutralization Test Using Recombinant Pestiviruses Possessing a Small Reporter Tag

by Madoka Tetsuo, Keita Matsuno, Tomokazu Tamura, Takasuke Fukuhara, Taksoo Kim, Masatoshi Okamatsu, Norbert Tautz, Yoshiharu Matsuura and Yoshihiro Sakoda

Pathogens 2020, 9(3), 188; https://doi.org/10.3390/pathogens9030188 - 4 Mar 2020

Cited by 15 | Viewed by 6682

Abstract

A serum neutralization test (SNT) is an essential method for the serological diagnosis of pestivirus infections, including classical swine fever, because of the cross reactivity of antibodies against pestiviruses and the non-quantitative properties of antibodies in an enzyme-linked immunosorbent assay. In conventional SNTs, [...] Read more.

A serum neutralization test (SNT) is an essential method for the serological diagnosis of pestivirus infections, including classical swine fever, because of the cross reactivity of antibodies against pestiviruses and the non-quantitative properties of antibodies in an enzyme-linked immunosorbent assay. In conventional SNTs, an immunoperoxidase assay or observation of cytopathic effect after incubation for 3 to 7 days is needed to determine the SNT titer, which requires labor-intensive or time-consuming procedures. Therefore, a new SNT, based on the luciferase system and using classical swine fever virus, bovine viral diarrhea virus, and border disease virus possessing the 11-amino-acid subunit derived from NanoLuc luciferase was developed and evaluated; this approach enabled the rapid and easy determination of the SNT titer using a luminometer. In the new method, SNT titers can be determined tentatively at 2 days post-infection (dpi) and are comparable to those obtained by conventional SNTs at 3 or 4 dpi. In conclusion, the luciferase-based SNT can replace conventional SNTs as a high-throughput antibody test for pestivirus infections. Full article

(This article belongs to the Special Issue Classical Swine Fever)

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13 pages, 1350 KB

Open AccessEditor’s ChoiceArticle

Phylogenetic Analysis of Belgian Small Ruminant Lentiviruses Supports Cross Species Virus Transmission and Identifies New Subtype B5 Strains

by Rodolphe Michiels, Nadjah Radia Adjadj and Nick De Regge

Pathogens 2020, 9(3), 183; https://doi.org/10.3390/pathogens9030183 - 3 Mar 2020

Cited by 38 | Viewed by 3434

Abstract

Small ruminant lentiviruses (SRLV) are a group of highly divergent viruses responsible for global and fatal infections in sheep and goats. Since the current phylogenetic classification of these viruses was proposed in 2004, it nowadays consists out of 5 genotypes and 28 subtypes. [...] Read more.

Small ruminant lentiviruses (SRLV) are a group of highly divergent viruses responsible for global and fatal infections in sheep and goats. Since the current phylogenetic classification of these viruses was proposed in 2004, it nowadays consists out of 5 genotypes and 28 subtypes. In support of our national SRLV control program, we performed the genetic characterization of SRLV strains circulating in the Belgian sheep and goat population. Fourteen sheep and 9 goat strains were sequenced in the gag-pol and pol regions using the method described by Shah. Most SRLV strains from sheep and goats belonged to prototype A1 and B1 subtypes, respectively. We, however, also found indications for cross-species transmission of SRLV strains between sheep and goats and vice versa, and identified a new subtype designated as B5. An in-depth analysis of the current SRLV phylogeny revealed that many subtypes have been defined over the years based on limited sequence information. To keep phylogeny as a useful tool, we advocate to apply more rigorous sequencing standards to ensure the correct classification of current and new emerging strains. The genetic characterization of Belgian SRLV strains will help in the development of appropriate diagnostic tools to assist the national control program. Full article

(This article belongs to the Section Animal Pathogens)

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26 pages, 3075 KB

Open AccessFeature PaperEditor’s ChoiceReview

Aggregatibacter, a Low Abundance Pathobiont That Influences Biogeography, Microbial Dysbiosis, and Host Defense Capabilities in Periodontitis: The History of a Bug, and Localization of Disease

by Daniel H. Fine, Helen Schreiner and Senthil Kumar Velusamy

Pathogens 2020, 9(3), 179; https://doi.org/10.3390/pathogens9030179 - 2 Mar 2020

Cited by 29 | Viewed by 5365

Abstract

Aggregatibacter actinomycetemcomitans, the focus of this review, was initially proposed as a microbe directly related to a phenotypically distinct form of periodontitis called localized juvenile periodontitis. At the time, it seemed as if specific microbes were implicated as the cause of distinct forms [...] Read more.

Aggregatibacter actinomycetemcomitans, the focus of this review, was initially proposed as a microbe directly related to a phenotypically distinct form of periodontitis called localized juvenile periodontitis. At the time, it seemed as if specific microbes were implicated as the cause of distinct forms of disease. Over the years, much has changed. The sense that specific microbes relate to distinct forms of disease has been challenged, as has the sense that distinct forms of periodontitis exist. This review consists of two components. The first part is presented as a detective story where we attempt to determine what role, if any, Aggregatibacter plays as a participant in disease. The second part describes landscape ecology in the context of how the host environment shapes the framework of local microbial dysbiosis. We then conjecture as to how the local host response may limit the damage caused by pathobionts. We propose that the host may overcome the constant barrage of a dysbiotic microbiota by confining it to a local tooth site. We conclude speculating that the host response can confine local damage by restricting bacteremic translocation of members of the oral microbiota to distant organs thus constraining morbidity and mortality of the host. Full article

(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)

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37 pages, 2829 KB

Open AccessEditor’s ChoiceArticle

Upscaling the Surveillance of Tick-Borne Pathogens in the French Caribbean Islands

by Mathilde Gondard, Sabine Delannoy, Valérie Pinarello, Rosalie Aprelon, Elodie Devillers, Clémence Galon, Jennifer Pradel, Muriel Vayssier-Taussat, Emmanuel Albina and Sara Moutailler

Pathogens 2020, 9(3), 176; https://doi.org/10.3390/pathogens9030176 - 1 Mar 2020

Cited by 23 | Viewed by 4640

Abstract

Despite the high burden of vector-borne disease in (sub)tropical areas, few information are available regarding the diversity of tick and tick-borne pathogens circulating in the Caribbean. Management and control of vector-borne disease require actual epidemiological data to better assess and anticipate the risk [...] Read more.

Despite the high burden of vector-borne disease in (sub)tropical areas, few information are available regarding the diversity of tick and tick-borne pathogens circulating in the Caribbean. Management and control of vector-borne disease require actual epidemiological data to better assess and anticipate the risk of (re)emergence of tick-borne diseases in the region. To simplify and reduce the costs of such large-scale surveys, we implemented a high-throughput microfluidic real-time PCR system suitable for the screening of the main bacterial and parasitic genera involved in tick-borne disease and potentially circulating in the area. We used the new screening tool to perform an exploratory epidemiological study on 132 adult specimens of Amblyomma variegatum and 446 of Rhipicephalus microplus collected in Guadeloupe and Martinique. Not only the system was able to detect the main pathogens of the area—Ehrlichia ruminantium, Rickettsia africae, Anaplasma marginale, Babesia bigemina and Babesia bovis—but the system also provided evidence of unsuspected microorganisms in Caribbean ticks, belonging to the Anaplasma, Ehrlichia, Borrelia and Leishmania genera. Our study demonstrated how high-throughput microfluidic real-time PCR technology can assist large-scale epidemiological studies, providing a rapid overview of tick-borne pathogen and microorganism diversity, and opening up new research perspectives for the epidemiology of tick-borne pathogens. Full article

(This article belongs to the Collection Advances in Tick Research)

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8 pages, 832 KB

Open AccessEditor’s ChoiceArticle

MmpS5-MmpL5 Transporters Provide Mycobacterium smegmatis Resistance to imidazo[1,2-b][1,2,4,5]tetrazines

by Dmitry A. Maslov, Kirill V. Shur, Aleksey A. Vatlin and Valery N. Danilenko

Pathogens 2020, 9(3), 166; https://doi.org/10.3390/pathogens9030166 - 28 Feb 2020

Cited by 17 | Viewed by 4424

Abstract

The emergence and spread of drug-resistant Mycobacterium tuberculosis strains (including MDR, XDR, and TDR) force scientists worldwide to search for new anti-tuberculosis drugs. We have previously reported a number of imidazo[1,2-b][1,2,4,5]tetrazines – putative inhibitors of mycobacterial eukaryotic-type serine-threonine protein-kinases, active against [...] Read more.

The emergence and spread of drug-resistant Mycobacterium tuberculosis strains (including MDR, XDR, and TDR) force scientists worldwide to search for new anti-tuberculosis drugs. We have previously reported a number of imidazo[1,2-b][1,2,4,5]tetrazines – putative inhibitors of mycobacterial eukaryotic-type serine-threonine protein-kinases, active against M. tuberculosis. Whole genomic sequences of spontaneous drug-resistant M. smegmatis mutants revealed four genes possibly involved in imidazo[1,2-b][1,2,4,5]tetrazines resistance; however, the exact mechanism of resistance remain unknown. We used different approaches (construction of targeted mutants, overexpression of the wild-type (w.t.) and mutant genes, and gene-expression studies) to assess the role of the previously identified mutations. We show that mutations in MSMEG_1380 gene lead to overexpression of the mmpS5-mmpL5 operon in M. smegmatis, thus providing resistance to imidazo[1,2-b][1,2,4,5]tetrazines by increased efflux through the MmpS5-MmpL5 system, similarly to the mechanisms of resistance described for M. tuberculosis and M. abscessus. Mycobacterial MmpS5-MmpL5 transporters should be considered as an MDR-efflux system and they should be taken into account at early stages of anti-tuberculosis drug development. Full article

(This article belongs to the Special Issue Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment)

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12 pages, 3197 KB

Open AccessEditor’s ChoiceArticle

Pathogenicity and Genetic Characterization of Vietnamese Classical Swine Fever Virus: 2014–2018

by SeEun Choe, Van Phan Le, Jihye Shin, Jae-Hoon Kim, Ki-Sun Kim, Sok Song, Ra Mi Cha, Gyu-Nam Park, Thi Lan Nguyen, Bang-Hun Hyun, Bong-Kyun Park and Dong-Jun An

Pathogens 2020, 9(3), 169; https://doi.org/10.3390/pathogens9030169 - 28 Feb 2020

Cited by 18 | Viewed by 4199

Abstract

Here, we examined the pathogenicity and genetic differences between classical swine fever viruses (CSFV) isolated on pig farms in North Vietnam from 2014–2018. Twenty CSFV strains from 16 pig farms were classified as genotype 2 (sub-genotypes 2.1b, 2.1c, and 2.2). The main sub-genotype, [...] Read more.

Here, we examined the pathogenicity and genetic differences between classical swine fever viruses (CSFV) isolated on pig farms in North Vietnam from 2014–2018. Twenty CSFV strains from 16 pig farms were classified as genotype 2 (sub-genotypes 2.1b, 2.1c, and 2.2). The main sub-genotype, 2.1c, was classified phylogenetically as belonging to the same cluster as viruses isolated from the Guangdong region in South China. Strain HY58 (sub-genotype 2.1c), isolated from pigs in Vietnam, caused higher mortality (60%) than the Vietnamese ND20 strain (sub-genotype 2.2). The Vietnamese strain of sub-genotype 2.1b was estimated to have moderate virulence; indeed, genetic analysis revealed that it belongs to the same cluster as Korean CSFV sub-genotype 2.1b. Most CSFVs circulating in North Vietnam belong to sub-genotype 2.1c. Geographical proximity means that this genotype might continue to circulate in both North Vietnam and Southern China (Guangdong, Guangxi, and Hunan). Full article

(This article belongs to the Special Issue Classical Swine Fever)

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