Pathogens

16 pages, 3419 KiB

Open AccessArticle

Catalase and Ascorbate Peroxidase in Euglenozoan Protists

by Ingrid Škodová-Sveráková, Kristína Záhonová, Barbora Bučková, Zoltán Füssy, Vyacheslav Yurchenko and Julius Lukeš

Pathogens 2020, 9(4), 317; https://doi.org/10.3390/pathogens9040317 - 24 Apr 2020

Cited by 11 | Viewed by 3451

Abstract

In this work, we studied the biochemical properties and evolutionary histories of catalase (CAT) and ascorbate peroxidase (APX), two central enzymes of reactive oxygen species detoxification, across the highly diverse clade Eugenozoa. This clade encompasses free-living phototrophic and heterotrophic flagellates, as well as [...] Read more.

In this work, we studied the biochemical properties and evolutionary histories of catalase (CAT) and ascorbate peroxidase (APX), two central enzymes of reactive oxygen species detoxification, across the highly diverse clade Eugenozoa. This clade encompasses free-living phototrophic and heterotrophic flagellates, as well as obligate parasites of insects, vertebrates, and plants. We present evidence of several independent acquisitions of CAT by horizontal gene transfers and evolutionary novelties associated with the APX presence. We posit that Euglenozoa recruit these detoxifying enzymes for specific molecular tasks, such as photosynthesis in euglenids and membrane-bound peroxidase activity in kinetoplastids and some diplonemids. Full article

(This article belongs to the Special Issue Kinetoplastid Phylogenomics and Evolution)

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17 pages, 3831 KiB

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 16 | Viewed by 6370

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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13 pages, 2502 KiB

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 28 | Viewed by 4569

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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16 pages, 2976 KiB

Open AccessCase Report

Salmonella Typhimurium Triggered Unilateral Epididymo-Orchitis and Splenomegaly in a Holstein Bull in Assiut, Egypt: A Case Report

by Manal A. M. Mahmoud, Gaber Megahed, Mohamed S. Yousef, Fatma Abo Zakaib Ali, Rania S. Zaki and Hanan H. Abdelhafeez

Pathogens 2020, 9(4), 314; https://doi.org/10.3390/pathogens9040314 - 24 Apr 2020

Cited by 5 | Viewed by 3162

Abstract

This report illustrates, for the first time, a case of unilateral orchitis and epididymitis in a Holstein-Friesian bull, associated with Salmonella enterica infection (Salmonella enterica serovar Typhimurium). A one and a half-year-old Holstein-Friesian bull had arrived at the Veterinary Hospital of Assiut [...] Read more.

This report illustrates, for the first time, a case of unilateral orchitis and epididymitis in a Holstein-Friesian bull, associated with Salmonella enterica infection (Salmonella enterica serovar Typhimurium). A one and a half-year-old Holstein-Friesian bull had arrived at the Veterinary Hospital of Assiut University suffering from anorexia accompanied with persistent fever, which did not respond to oxytetracycline and flunixin meglumine injection for 15 days. Gross examination revealed left scrotal enlargement (three times its normal size), heat sensation, and induration of the testis and epididymis, which was painful on external palpation. Microbiological and pathological examinations of the left testicle, epididymis, and spleen samples were performed. S. Typhimurium was recovered from the affected tissues and its critical virulence genes (stn, avrA and sopB) were identified. Pathological examination revealed a unilateral necrotizing intratubular pyogranulomatus orchitis and epididymitis with severe peri-orchitis. In addition, splenomegaly with a firm and large whitish nodular capsular structure associated with different stages of granulomatous reaction around the white and red pulp. To the authors’ knowledge, this report is the first isolation of S. Typhimurium from the epididymis and testicles of a Holstein-Friesian bull. These results highlight the importance of including S. Typhimurium among the health disorders associated with stressful situations in bovine with orchitis and or/epididymitis. In Egypt, Salmonella spp. infection as being enzootic with high probability of dissemination should be considered one of genital health problems among cattle farms. Full article

(This article belongs to the Section Animal Pathogens)

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4 pages, 183 KiB

Open AccessEditorial

Oral Microbiota: Discovering and Facing the New Associations with Systemic Diseases

by Romeo Patini

Pathogens 2020, 9(4), 313; https://doi.org/10.3390/pathogens9040313 - 24 Apr 2020

Cited by 10 | Viewed by 2384

Abstract

The economic crisis of the first decades of the 2000s had serious repercussions on the economy of individual countries, producing a gradual impoverishment of populations. The reduction in financial resources has significantly reduced citizens’ access to care, forcing them to abandon preventive medicine [...] Read more.

The economic crisis of the first decades of the 2000s had serious repercussions on the economy of individual countries, producing a gradual impoverishment of populations. The reduction in financial resources has significantly reduced citizens’ access to care, forcing them to abandon preventive medicine treatments and check-ups. The health of the oral cavity, which had long been considered of secondary importance when compared with systemic pathologies whose course can be potentially fatal for the patient, has therefore been strongly neglected. In recent years, however, new mechanisms of etiology of systemic diseases have been studied with the aim of evaluating some aspects still unknown. The microbiota, whose interest has grown considerably in the national scientific community, was immediately considered as a key factor in the pathogenesis of some disorders. These analyses have also benefited from numerous advances in the field of crop and molecular diagnostics in the microbiological field. Although pioneering studies have focused on the microbiota of the gastro-intestinal system, subsequent evidence has also been drawn from various studies conducted on the oral microbiota. What emerged is that oral microbiota dysbiosis has been associated with numerous systemic diseases. Therefore, the purpose of this Special Issue is to encourage scientific research on the topic of the relationship between the oral microbiota and systemic diseases, also inviting the use of new techniques for culture and molecular diagnosis. Particular attention will be given to original works in vivo and to literature reviews provided they are carried out with a systematic approach and, if possible, supported by additional quantitative analyses. Full article

(This article belongs to the Special Issue New Diagnostic and Treatment Techniques of Oral Microbiota)

25 pages, 2278 KiB

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 209 | Viewed by 13930

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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9 pages, 1207 KiB

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 15 | Viewed by 3770

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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26 pages, 4754 KiB

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 76 | Viewed by 14934

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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17 pages, 2700 KiB

Open AccessArticle

Resistance of Tick Gut Microbiome to Anti-Tick Vaccines, Pathogen Infection and Antimicrobial Peptides

by Agustín Estrada-Peña, Alejandro Cabezas-Cruz and Dasiel Obregón

Pathogens 2020, 9(4), 309; https://doi.org/10.3390/pathogens9040309 - 22 Apr 2020

Cited by 28 | Viewed by 5255

Abstract

Ixodes scapularis ticks harbor microbial communities including pathogenic and non-pathogenic microbes. Pathogen infection increases the expression of several tick gut proteins, which disturb the tick gut microbiota and impact bacterial biofilm formation. Anaplasma phagocytophilum induces ticks to express I. scapularis antifreeze glycoprotein (IAFGP), [...] Read more.

Ixodes scapularis ticks harbor microbial communities including pathogenic and non-pathogenic microbes. Pathogen infection increases the expression of several tick gut proteins, which disturb the tick gut microbiota and impact bacterial biofilm formation. Anaplasma phagocytophilum induces ticks to express I. scapularis antifreeze glycoprotein (IAFGP), a protein with antimicrobial activity, while Borrelia burgdorferi induces the expression of PIXR. Here, we tested the resistance of I. scapularis microbiome to A. phagocytophilum infection, antimicrobial peptide IAFGP, and anti-tick immunity specific to PIXR. We demonstrate that A. phagocytophilum infection and IAFGP affect the taxonomic composition and taxa co-occurrence networks, but had limited impact on the functional traits of tick microbiome. In contrast, anti-tick immunity disturbed the taxonomic composition and the functional profile of tick microbiome, by increasing both the taxonomic and pathways diversity. Mechanistically, we show that anti-tick immunity increases the representation and importance of the polysaccharide biosynthesis pathways involved in biofilm formation, while these pathways are under-represented in the microbiome of ticks infected by A. phagocytophilum or exposed to IAFGP. These analyses revealed that tick microbiota is highly sensitive to anti-tick immunity, while it is less sensitive to pathogen infection and antimicrobial peptides. Results suggest that biofilm formation may be a defensive response of tick microbiome to anti-tick immunity. Full article

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

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14 pages, 905 KiB

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 15 | Viewed by 5066

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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13 pages, 866 KiB

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 62 | Viewed by 16764

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, 1358 KiB

Open AccessArticle

Genetic Diversity and Recombination in the Plant Pathogen Sclerotinia sclerotiorum Detected in Sri Lanka

by Thirega Mahalingam, Weidong Chen, Chandima Shashikala Rajapakse, Kandangamuwa Pathirannahalage Somachandra and Renuka Nilmini Attanayake

Pathogens 2020, 9(4), 306; https://doi.org/10.3390/pathogens9040306 - 22 Apr 2020

Cited by 6 | Viewed by 3368

Abstract

Sclerotinia sclerotiorum is an important fungal pathogen on many economically important crops including cabbage worldwide. Even though population structure and genetic diversity of S. sclerotiorum is well studied in temperate climatic conditions, only a few studies have been conducted in tropical countries. It [...] Read more.

Sclerotinia sclerotiorum is an important fungal pathogen on many economically important crops including cabbage worldwide. Even though population structure and genetic diversity of S. sclerotiorum is well studied in temperate climatic conditions, only a few studies have been conducted in tropical countries. It is also not clear whether the populations are clonal or recombining in the tropics. In filling this information gap, 47 isolates of S. sclerotiorum were collected from commercial cabbage (Brassica oleracea L.) fields in Nuwara Eliya district of Sri Lanka, where the disease has been previously reported. All the isolates were subjected to genetic diversity study using mycelial compatibility grouping and microsatellite markers. Fourteen mycelial compatibility groups (MCGs) and 23 multilocus haplotypes (MLHs) were recorded. Mean expected heterozygosity of the population was 0.56. MLHs were weakly correlated with MCGs. Population genetic structure analysis and principal coordinates identified three genetic clusters. Genetic recombination was inferred within each genetic cluster when isolates were subjected to clone correction. There was evidence of multiple infections on single plant as detected by the presence of more than one MCG on each cabbage plant. However, multiple infections did not increase the disease severity in detached leaf assay. We found high genetic diversity and recombination of S. sclerotiorum population in a tropical country, Sri Lanka. Importance of detecting genetic structure when inferring recombination was also highlighted. Full article

(This article belongs to the Section Plant Pathogens)

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12 pages, 409 KiB

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 24 | Viewed by 3383

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 KiB

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 13 | Viewed by 2972

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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15 pages, 2322 KiB

Open AccessArticle

GoPrime: Development of an In Silico Framework to Predict the Performance of Real-Time PCR Primers and Probes Using Foot-and-Mouth Disease Virus as a Model

by Emma L A Howson, Richard J Orton, Valerie Mioulet, Tiziana Lembo, Donald P King and Veronica L Fowler

Pathogens 2020, 9(4), 303; https://doi.org/10.3390/pathogens9040303 - 20 Apr 2020

Cited by 3 | Viewed by 3922

Abstract

Real-time PCR (rPCR) is a widely accepted diagnostic tool for the detection and quantification of nucleic acid targets. In order for these assays to achieve high sensitivity and specificity, primer and probe-template complementarity is essential; however, mismatches are often unavoidable and can result [...] Read more.

Real-time PCR (rPCR) is a widely accepted diagnostic tool for the detection and quantification of nucleic acid targets. In order for these assays to achieve high sensitivity and specificity, primer and probe-template complementarity is essential; however, mismatches are often unavoidable and can result in false-negative results and errors in quantifying target sequences. Primer and probe sequences therefore require continual evaluation to ensure they remain fit for purpose. This paper describes the development of a linear model and associated computational tool (GoPrime) designed to predict the performance of rPCR primers and probes across multiple sequence data. Empirical data were generated using DNA oligonucleotides (n = 90) that systematically introduced variation in the primer and probe target regions of a diagnostic assay routinely used to detect foot-and-mouth disease virus (FMDV); an animal virus that exhibits a high degree of sequence variability. These assays revealed consistent impacts of patterns of substitutions in primer and probe-sites on rPCR cycle threshold (C_T) and limit of detection (LOD). These data were used to populate GoPrime, which was subsequently used to predict rPCR results for DNA templates (n = 7) representing the natural sequence variability within FMDV. GoPrime was also applicable to other areas of the FMDV genome, with predictions for the likely targets of a FMDV-typing assay consistent with published experimental data. Although further work is required to improve these tools, including assessing the impact of primer-template mismatches in the reverse transcription step and the broader impact of mismatches for other assays, these data support the use of mathematical models for rapidly predicting the performance of rPCR primers and probes in silico. Full article

(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)

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23 pages, 1913 KiB

Open AccessArticle

Risk Assessment of African Swine Fever Virus Exposure to Sus scrofa in Japan Via Pork Products Brought in Air Passengers’ Luggage

by Satoshi Ito, Jaime Bosch, Cristina Jurado, José Manuel Sánchez-Vizcaíno and Norikazu Isoda

Pathogens 2020, 9(4), 302; https://doi.org/10.3390/pathogens9040302 - 20 Apr 2020

Cited by 11 | Viewed by 3800

Abstract

In recent years, African swine fever (ASF) has become prevalent in many areas, including Asia. The repeated detection of the ASF virus (ASFV) genome in pork products brought in air passenger’s luggage (PPAP) was also reported from Japanese airports. In the present study, [...] Read more.

In recent years, African swine fever (ASF) has become prevalent in many areas, including Asia. The repeated detection of the ASF virus (ASFV) genome in pork products brought in air passenger’s luggage (PPAP) was also reported from Japanese airports. In the present study, the risk of ASFV exposure to susceptible hosts in Japan via three different pathways was assessed. Two quantitative stochastic risk assessment models were built to estimate the annual probability of ASFV exposure to domestic pigs, which could be attributed to foreign job trainees or foreign tourists. A semi-quantitative stochastic model was built to assess the risk of ASFV exposure to wild boar caused by foreign tourists. The overall mean annual probability of ASFV exposure to domestic pigs via PPAP carried by foreign job trainees was 0.169 [95% confidence interval (CI): 0.000–0.600], whereas that by foreign tourists was 0.050 [95% CI: 0.000–0.214], corresponding to approximately one introduction every 5.9 and 20 years, respectively. The risk of ASFV exposure to domestic pigs was dispersed over the country, whereas that of wild boar was generally higher in the western part of Japan, indicating that the characteristics of the potential ASF risk in each prefecture were varied. Full article

(This article belongs to the Special Issue African Swine Fever Virus Infection)

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83 pages, 7065 KiB

Open AccessArticle

Systematic Review of Important Viral Diseases in Africa in Light of the ‘One Health’ Concept

by Ravendra P. Chauhan, Zelalem G. Dessie, Ayman Noreddin and Mohamed E. El Zowalaty

Pathogens 2020, 9(4), 301; https://doi.org/10.3390/pathogens9040301 - 20 Apr 2020

Cited by 33 | Viewed by 10081

Abstract

Emerging and re-emerging viral diseases are of great public health concern. The recent emergence of Severe Acute Respiratory Syndrome (SARS) related coronavirus (SARS-CoV-2) in December 2019 in China, which causes COVID-19 disease in humans, and its current spread to several countries, leading to [...] Read more.

Emerging and re-emerging viral diseases are of great public health concern. The recent emergence of Severe Acute Respiratory Syndrome (SARS) related coronavirus (SARS-CoV-2) in December 2019 in China, which causes COVID-19 disease in humans, and its current spread to several countries, leading to the first pandemic in history to be caused by a coronavirus, highlights the significance of zoonotic viral diseases. Rift Valley fever, rabies, West Nile, chikungunya, dengue, yellow fever, Crimean-Congo hemorrhagic fever, Ebola, and influenza viruses among many other viruses have been reported from different African countries. The paucity of information, lack of knowledge, limited resources, and climate change, coupled with cultural traditions make the African continent a hotspot for vector-borne and zoonotic viral diseases, which may spread globally. Currently, there is no information available on the status of virus diseases in Africa. This systematic review highlights the available information about viral diseases, including zoonotic and vector-borne diseases, reported in Africa. The findings will help us understand the trend of emerging and re-emerging virus diseases within the African continent. The findings recommend active surveillance of viral diseases and strict implementation of One Health measures in Africa to improve human public health and reduce the possibility of potential pandemics due to zoonotic viruses. Full article

(This article belongs to the Section Animal Pathogens)

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20 pages, 640 KiB

Open AccessReview

Human Papillomaviruses and Epstein–Barr Virus Interactions in Colorectal Cancer: A Brief Review

by Queenie Fernandes, Ishita Gupta, Semir Vranic and Ala-Eddin Al Moustafa

Pathogens 2020, 9(4), 300; https://doi.org/10.3390/pathogens9040300 - 20 Apr 2020

Cited by 21 | Viewed by 4403

Abstract

Human papillomaviruses (HPVs) and the Epstein–Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%–15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and [...] Read more.

Human papillomaviruses (HPVs) and the Epstein–Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%–15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and progression of several human carcinomas, including head and neck, cervical and colorectal. Oncoproteins of high-risk HPVs and EBV can cooperate to initiate and/or enhance epithelial-mesenchymal transition (EMT) events, which represents one of the hallmarks of cancer progression and metastasis. Although the role of these oncoviruses in several cancers is well established, their role in the pathogenesis of colorectal cancer is still nascent. This review presents an overview of the most recent advances related to the presence and role of high-risk HPVs and EBV in colorectal cancer, with an emphasis on their cooperation in colorectal carcinogenesis. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction in Colorectal Carcinogenesis)

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13 pages, 2953 KiB

Open AccessArticle

Ethylicin Prevents Potato Late Blight by Disrupting Protein Biosynthesis of Phytophthora infestans

by Shumin Zhang, Meiquan Zhang, A. Rehman Khalid, Linxuan Li, Yang Chen, Pan Dong, Hanyan Wang and Maozhi Ren

Pathogens 2020, 9(4), 299; https://doi.org/10.3390/pathogens9040299 - 19 Apr 2020

Cited by 10 | Viewed by 3298

Abstract

Phytophthora infestans, the causal agent of potato late blight, triggered the devastating Great Irish Famine that lasted from 1845 to 1852. Today, it is still the greatest threat to the potato yield. Ethylicin is a broad-spectrum biomimetic-fungicide. However, its application in the [...] Read more.

Phytophthora infestans, the causal agent of potato late blight, triggered the devastating Great Irish Famine that lasted from 1845 to 1852. Today, it is still the greatest threat to the potato yield. Ethylicin is a broad-spectrum biomimetic-fungicide. However, its application in the control of Phytophthora infestans is still unknown. In this study, we investigated the effects of ethylicin on Phytophthora infestans. We found that ethylicin inhibited the mycelial growth, sporulation capacity, spore germination and virulence of Phytophthora infestans. Furthermore, the integrated analysis of proteomics and metabolomics indicates that ethylicin may inhibit peptide or protein biosynthesis by suppressing both the ribosomal function and amino acid metabolism, causing an inhibitory effect on Phytophthora infestans. These observations indicate that ethylicin may be an anti-oomycete agent that can be used to control Phytophthora infestans. Full article

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11 pages, 2998 KiB

Open AccessArticle

Effect of Sugars on Chlamydia trachomatis Infectivity

by Giacomo Marziali, Antonella Marangoni, Claudio Foschi, Maria Carla Re and Natalia Calonghi

Pathogens 2020, 9(4), 298; https://doi.org/10.3390/pathogens9040298 - 17 Apr 2020

Cited by 2 | Viewed by 2516

Abstract

Background. Previous works suggest that sugars can have a beneficial effect on C. trachomatis (CT) survival and virulence. In this study, we investigated the effect of different sugars on CT infectivity, elucidating some of the molecular mechanisms behind CT-sugar interaction. Methods. CT infectivity [...] Read more.

Background. Previous works suggest that sugars can have a beneficial effect on C. trachomatis (CT) survival and virulence. In this study, we investigated the effect of different sugars on CT infectivity, elucidating some of the molecular mechanisms behind CT-sugar interaction. Methods. CT infectivity was investigated on HeLa cells after 2 hour-incubation of elementary bodies (EBs) with glucose, sucrose, or mannitol solutions (0.5, 2.5, 5.0 mM). The effect of sugars on EB membrane fluidity was investigated by fluorescence anisotropy measurement, whereas the changes in lipopolysaccharide (LPS) exposure were examined by cytofluorimetric analysis. By means of a Western blot, we explored the phosphorylation state of Focal Adhesion Kinase (FAK) in HeLa cells infected with EBs pre-incubated with sugars. Results. All sugar solutions significantly increased CT infectivity on epithelial cells, acting directly on the EB structure. Sugars induced a significant increase of EB membrane fluidity, leading to changes in LPS membrane exposure. Especially after incubation with sucrose and mannitol, EBs led to a higher FAK phosphorylation, enhancing the activation of anti-apoptotic and proliferative signals in the host cells. Conclusions. Sugars can increase CT infectivity and virulence, by modulating the expression/exposure of chlamydial membrane ligands. Further in-depth studies are needed to better understand the molecular mechanisms involved. Full article

(This article belongs to the Special Issue Chlamydia trachomatis Infections)

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11 pages, 1018 KiB

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 37 | Viewed by 8758

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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22 pages, 6760 KiB

Open AccessArticle

In Vivo Antimicrobial and Wound-Healing Activity of Resveratrol, Dihydroquercetin, and Dihydromyricetin against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans

by Alexei B. Shevelev, Nicola La Porta, Elena P. Isakova, Stefan Martens, Yulia K. Biryukova, Alexander S. Belous, Dmitrii A. Sivokhin, Elena V. Trubnikova, Marina V. Zylkova, Alla V. Belyakova, Maria S. Smirnova and Yulia I. Deryabina

Pathogens 2020, 9(4), 296; https://doi.org/10.3390/pathogens9040296 - 17 Apr 2020

Cited by 43 | Viewed by 4421

Abstract

An increase in the spread of antibiotic-resistant opportunistic microorganisms causes serious problems in the treatment of purulent infections, burns, and trophic ulcers. We tested the antimicrobial activity in vivo of three polyphenols, Resveratrol, Dihydroquercetin (Taxifolin), and Dihydromyricetin (Ampelopsin) from Norway spruce bark to [...] Read more.

An increase in the spread of antibiotic-resistant opportunistic microorganisms causes serious problems in the treatment of purulent infections, burns, and trophic ulcers. We tested the antimicrobial activity in vivo of three polyphenols, Resveratrol, Dihydroquercetin (Taxifolin), and Dihydromyricetin (Ampelopsin) from Norway spruce bark to promote the elimination of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans from wounds. Purulent infection was modelled on wounds in rats infected with suspensions containing 10⁹ CFU (colony-forming unit)/mL of pathogens. The wound area was treated daily with solutions of the polyphenols or placebo for 14 days after the beginning of the treatment. The animals were examined daily, and each stage of the wound healing (inflammation, granulation, and maturation (marginal epithelialisation) was documented. The planimetric analysis of the wound recovery percentage was performed on the 3rd, 10th, and 14th day after the start of curing. Then, one echelon (three or four animals from each subgroup) was withdrawn from the experiment on days 3 (three animals), 10 (three animals), and 14 (four animals) for microscopy analysis of cytological composition of their wound defects by microscopy and microbiological analysis of their contamination with pathogens. Our results show that they are also able to suppress mast cell infiltration and stimulate lymphocyte and macrophage (monocyte) infiltration into the wound. Resveratrol stimulated the replacement of the scar with normal tissue (with a clear boundary between the dermis and epidermis) and the restoration of hair follicles. Resveratrol turned out to be significantly better than some commercial antimicrobial (Levomecol) and antifungal (Clotrimazole) ointments and can be proposed as a promising drug for topical use for the treatment of trophic ulcers and burns. Full article

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

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13 pages, 1620 KiB

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 26 | Viewed by 2834

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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20 pages, 1295 KiB

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 38 | Viewed by 6348

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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15 pages, 932 KiB

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 10 | Viewed by 4014

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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17 pages, 1214 KiB

Open AccessArticle

Impact of Bacteriophage-Supplemented Drinking Water on the E. coli Population in the Chicken Gut

by Sophie Kittler, Ruth Mengden, Imke H. E. Korf, Anna Bierbrodt, Johannes Wittmann, Madeleine Plötz, Arne Jung, Tatiana Lehnherr, Christine Rohde, Hansjörg Lehnherr, Günter Klein and Corinna Kehrenberg

Pathogens 2020, 9(4), 293; https://doi.org/10.3390/pathogens9040293 - 16 Apr 2020

Cited by 13 | Viewed by 3003

Abstract

Among intestinal coliform microbes in the broiler gut, there are potentially pathogenic Escherichia (E.) coli that can cause avian colibacillosis. The treatment with antibiotics favors the selection of multidrug-resistant bacteria and an alternative to this treatment is urgently required. A chicken [...] Read more.

Among intestinal coliform microbes in the broiler gut, there are potentially pathogenic Escherichia (E.) coli that can cause avian colibacillosis. The treatment with antibiotics favors the selection of multidrug-resistant bacteria and an alternative to this treatment is urgently required. A chicken model of intestinal colonization with an apathogenic model strain of E. coli was used to test if oral phage application can prevent or reduce the gut colonization of extraintestinal pathogenic E. coli variants in two individual experiments. The E. coli strain E28 was used as a model strain, which could be differentiated from other E. coli strains colonizing the broiler gut, and was susceptible to all cocktail phages applied. In the first trial, a mixture of six phages was continuously applied via drinking water. No reduction of the model E. coli strain E28 occurred, but phage replication could be demonstrated. In the second trial, the applied mixture was limited to the four phages, which showed highest efficacy in vitro. E. coli colonization was reduced in this trial, but again, no reduction of the E. coli strain E28 was observed. The results of the trials presented here can improve the understanding of the effect of phages on single strains in the multi-strain microbiota of the chicken gut. Full article

(This article belongs to the Section Vaccines and Therapeutic Developments)

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12 pages, 248 KiB

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 17 | Viewed by 3824

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)

13 pages, 3091 KiB

Open AccessArticle

Listeria monocytogenes Wall Teichoic Acid Glycosylation Promotes Surface Anchoring of Virulence Factors, Resistance to Antimicrobial Peptides, and Decreased Susceptibility to Antibiotics

by Diana Meireles, Rita Pombinho, Filipe Carvalho, Sandra Sousa and Didier Cabanes

Pathogens 2020, 9(4), 290; https://doi.org/10.3390/pathogens9040290 - 16 Apr 2020

Cited by 11 | Viewed by 3419

Abstract

The cell wall of Listeria monocytogenes (Lm), a major intracellular foodborne bacterial pathogen, comprises a thick peptidoglycan layer that serves as a scaffold for glycopolymers such as wall teichoic acids (WTAs). WTAs contain non-essential sugar substituents whose absence prevents bacteriophage [...] Read more.

The cell wall of Listeria monocytogenes (Lm), a major intracellular foodborne bacterial pathogen, comprises a thick peptidoglycan layer that serves as a scaffold for glycopolymers such as wall teichoic acids (WTAs). WTAs contain non-essential sugar substituents whose absence prevents bacteriophage binding and impacts antigenicity, sensitivity to antimicrobials, and virulence. Here, we demonstrated, for the first time, the triple function of Lm WTA glycosylations in the following: (1) supporting the correct anchoring of major Lm virulence factors at the bacterial surface, namely Ami and InlB; (2) promoting Lm resistance to antimicrobial peptides (AMPs); and (3) decreasing Lm sensitivity to some antibiotics. We showed that while the decoration of WTAs by rhamnose in Lm serovar 1/2a and by galactose in serovar 4b are important for the surface anchoring of Ami and InlB, N-acetylglucosamine in serovar 1/2a and glucose in serovar 4b are dispensable for the surface association of InlB or InlB/Ami. We found that the absence of a single glycosylation only had a slight impact on the sensibility of Lm to AMPs and antibiotics, however the concomitant deficiency of both glycosylations (rhamnose and N-acetylglucosamine in serovar 1/2a, and galactose and glucose in serovar 4b) significantly impaired the Lm capacity to overcome the action of antimicrobials. We propose WTA glycosylation as a broad mechanism used by Lm, not only to properly anchor surface virulence factors, but also to resist AMPs and antibiotics. WTA glycosyltransferases thus emerge as promising drug targets to attenuate the virulence of bacterial pathogens, while increasing their susceptibility to host immune defenses and potentiating the action of antibiotics. Full article

(This article belongs to the Special Issue Advances on Control of Foodborne Pathogens: From Conventional to Cutting-Edge Approaches)

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8 pages, 242 KiB

Open AccessArticle

Prevention of Intramammary Infections by Prepartum External Application of a Teat Dip Containing Lactic Acid Bacteria with Antimicrobial Properties in Dairy Heifers

by Jan-Hendrik Paduch, Johanna Lücking, Elisabeth Mansion-de Vries, Claudia Zinke, Nicole Wente and Volker Krömker

Pathogens 2020, 9(4), 288; https://doi.org/10.3390/pathogens9040288 - 16 Apr 2020

Cited by 1 | Viewed by 2741

Abstract

The aim of the current study was to investigate the effects of the prepartum external treatment of teats with a combination of four lactic acid bacteria strains viz. Lactobacillus (Lb.) rhamnosus ATCC 7469, Lactococcus lactis subsp. lactis ATCC 11454, Lb. paracasei [...] Read more.

The aim of the current study was to investigate the effects of the prepartum external treatment of teats with a combination of four lactic acid bacteria strains viz. Lactobacillus (Lb.) rhamnosus ATCC 7469, Lactococcus lactis subsp. lactis ATCC 11454, Lb. paracasei 78/37 (DSM 26911), and Lb. plantarum 118/37 (DSM 26912) on the postcalving udder health of dairy heifers. The study used a split-udder design. Two weeks before the expected calving date, one of two contralateral teats of a teat pair was dipped with an aqueous suspension of lactic acid bacteria (final bacterial counts 8.40–8.47 log₁₀-transformed CFU/mL) once in a week until calving; the other teat of the pair was not treated. After calving, quarter foremilk samples were taken and investigated cyto-microbiologically. In total, 629 teat pairs of 319 heifers were included. There was an association between the treatment and intramammary infections caused by the major udder-pathogenic bacteria Staphylococcus aureus, Streptococcus dysgalactiae, and enterococci, as well as clinical mastitis in the first 100 days after calving. The present study indicates that intramammary infections with major pathogens and clinical mastitis may be prevented by regular prepartum external application of lactic acid bacteria in dairy heifers. Full article

(This article belongs to the Collection Mastitis in Dairy Ruminants)

17 pages, 1185 KiB

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 22 | Viewed by 5785

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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