Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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12 pages, 2307 KiB  
Article
The Surface Protein Fructose-1, 6 Bisphosphate Aldolase of Klebsiella pneumoniae Serotype K1: Role of Interaction with Neutrophils
by Chen-Hsiang Lee, Seng-Kee Chuah, Chia-Chi Chang and Fang-Ju Chen
Pathogens 2020, 9(12), 1009; https://doi.org/10.3390/pathogens9121009 - 30 Nov 2020
Cited by 16 | Viewed by 3352
Abstract
Hypermucoviscosity phenotypic Klebsiella pneumoniae (HV-Kp) serotype K1 is the predominant pathogen of a pyogenic liver abscess, an emerging infectious disease that often complicates septic metastatic syndrome in diabetic patients with poor sugar control. HV-Kpisolates were more resistant to neutrophil [...] Read more.
Hypermucoviscosity phenotypic Klebsiella pneumoniae (HV-Kp) serotype K1 is the predominant pathogen of a pyogenic liver abscess, an emerging infectious disease that often complicates septic metastatic syndrome in diabetic patients with poor sugar control. HV-Kpisolates were more resistant to neutrophil phagocytosis than non-HV-Kpisolates because of different pathogen-associated molecular patterns. The protein expression of HV-Kp after interaction with neutrophils is unclear. We studied KP-M1 (HV phenotype; serotype K1), DT-X (an acapsularmutant strain of KP-M1), and E. coli (ATCC 25922) with the model of Kp-infected neutrophils, using a comparative proteomic approach. One the identified protein, namely fructose-1, 6-bisphosphate aldolase (FBA), was found to be distributed in the KP-M1 after infecting neutrophils. Cell fractionation experiments showed that FBA is localized both to the cytoplasm and the outer membrane. Flow cytometry demonstrated that outer membrane-localized FBA was surface-accessible to FBA-specific antibody. The fba gene expression was enhanced in high glucose concentrations, which leads to increasing bacterial resistance to neutrophils phagocytosis and killing. The KP-M1 after FBA inhibitors and FBA-specific antibody treatment showed a significant reduction in bacterial resistance to neutrophils phagocytosis and killing, respectively, compared to KP-M1 without treatment. FBA is a highly conserved surface-exposed protein that is required for optimal interaction of HV-Kp to neutrophils. Full article
(This article belongs to the Collection Immunological Responses and Immune Defense Mechanism)
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21 pages, 2503 KiB  
Article
Gut Symbiotic Microbial Communities in the IUCN Critically Endangered Pinna nobilis Suffering from Mass Mortalities, Revealed by 16S rRNA Amplicon NGS
by Athanasios Lattos, Ioannis A. Giantsis, Dimitrios Karagiannis, John A. Theodorou and Basile Michaelidis
Pathogens 2020, 9(12), 1002; https://doi.org/10.3390/pathogens9121002 - 29 Nov 2020
Cited by 24 | Viewed by 3738
Abstract
Mass mortality events due to disease outbreaks have recently affected almost every healthy population of fan mussel, Pinna nobilis in Mediterranean Sea. The devastating mortality of the species has turned the interest of the research towards the causes of these events. After the [...] Read more.
Mass mortality events due to disease outbreaks have recently affected almost every healthy population of fan mussel, Pinna nobilis in Mediterranean Sea. The devastating mortality of the species has turned the interest of the research towards the causes of these events. After the haplosporidan infestation and the infection by Mycobacterium sp., new emerging pathogens have arisen based on the latest research. In the present study, a metagenomic approach of 16S rRNA next generation sequencing (NGS) was applied in order to assess the bacterial diversity within the digestive gland of diseased individuals as well as to carry out geographical correlations among the biodiversity of microbiome in the endangered species Pinna nobilis. The specimens originated from the mortalities occurred in 2019 in the region of Greece. Together with other bacterial genera, the results confirmed the presence of Vibrio spp., assuming synergistic effects in the mortality events of the species. Alongside with the presence of Vibrio spp., numerous bacterial genera were detected as well, including Aliivibrio spp., Photobacterium spp., Pseudoalteromonas spp., Psychrilyobacter spp. and Mycoplasma spp. Bacteria of the genus Mycoplasma were in high abundance particularly in the sample originated from Limnos island representing the first time recorded in Pinna nobilis. In conclusion, apart from exclusively the Haplosporidan and the Mycobacterium parasites, the presence of potentially pathogenic bacterial taxa detected, such as Vibrio spp., Photobactrium spp. and Alivibrio spp. lead us to assume that mortality events in the endangered Fan mussel, Pinna nobilis, may be attributed to synergistic effects of more pathogens. Full article
(This article belongs to the Special Issue Spontaneous Diseases of Mollusks)
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23 pages, 3204 KiB  
Article
A Paradox in Bacterial Pathogenesis: Activation of the Local Macrophage Inflammasome Is Required for Virulence of Streptococcus uberis
by Nathan Archer, Sharon A. Egan, Tracey J. Coffey, Richard D. Emes, M. Filippa Addis, Philip N. Ward, Adam M. Blanchard and James A. Leigh
Pathogens 2020, 9(12), 997; https://doi.org/10.3390/pathogens9120997 - 28 Nov 2020
Cited by 13 | Viewed by 4615
Abstract
Streptococcus uberis is a common cause of intramammary infection and mastitis in dairy cattle. Unlike other mammary pathogens, S. uberis evades detection by mammary epithelial cells, and the host–pathogen interactions during early colonisation are poorly understood. Intramammary challenge of dairy cows with S. [...] Read more.
Streptococcus uberis is a common cause of intramammary infection and mastitis in dairy cattle. Unlike other mammary pathogens, S. uberis evades detection by mammary epithelial cells, and the host–pathogen interactions during early colonisation are poorly understood. Intramammary challenge of dairy cows with S. uberis (strain 0140J) or isogenic mutants lacking the surface-anchored serine protease, SUB1154, demonstrated that virulence was dependent on the presence and correct location of this protein. Unlike the wild-type strain, the mutant lacking SUB1154 failed to elicit IL-1β from ex vivo CD14+ cells obtained from milk (bovine mammary macrophages, BMM), but this response was reinstated by complementation with recombinant SUB1154; the protein in isolation elicited no response. Production of IL-1β was ablated in the presence of various inhibitors, indicating dependency on internalisation and activation of NLRP3 and caspase-1, consistent with inflammasome activation. Similar transcriptomic changes were detected in ex vivo BMM in response to the wild-type or the SUB1154 deletion mutant, consistent with S. uberis priming BMM, enabling the SUB1154 protein to activate inflammasome maturation in a transcriptionally independent manner. These data can be reconciled in a novel model of pathogenesis in which, paradoxically, early colonisation is dependent on the innate response to the initial infection. Full article
(This article belongs to the Collection Mastitis in Dairy Ruminants)
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25 pages, 1149 KiB  
Review
The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections
by Alexey A. Lozhkov, Sergey A. Klotchenko, Edward S. Ramsay, Herman D. Moshkoff, Dmitry A. Moshkoff, Andrey V. Vasin and Maria S. Salvato
Pathogens 2020, 9(12), 989; https://doi.org/10.3390/pathogens9120989 - 26 Nov 2020
Cited by 29 | Viewed by 13160
Abstract
Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of [...] Read more.
Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection. Full article
(This article belongs to the Collection Immunological Responses and Immune Defense Mechanism)
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12 pages, 37488 KiB  
Article
Stability of African Swine Fever Virus in Soil and Options to Mitigate the Potential Transmission Risk
by Jolene Carlson, Melina Fischer, Laura Zani, Michael Eschbaumer, Walter Fuchs, Thomas Mettenleiter, Martin Beer and Sandra Blome
Pathogens 2020, 9(11), 977; https://doi.org/10.3390/pathogens9110977 - 23 Nov 2020
Cited by 52 | Viewed by 5609
Abstract
Understanding African swine fever virus (ASFV) transmission is essential for strategies to minimize virus spread during an outbreak. ASFV can survive for extended time periods in animal products, carcasses, and the environment. While the ASFV genome was found in environments around infected farms, [...] Read more.
Understanding African swine fever virus (ASFV) transmission is essential for strategies to minimize virus spread during an outbreak. ASFV can survive for extended time periods in animal products, carcasses, and the environment. While the ASFV genome was found in environments around infected farms, data on the virus survival in soil are scarce. We investigated different soil matrices spiked with ASFV-positive blood from infected wild boar to see if ASFV can remain infectious in the soil beneath infected carcasses. As expected, ASFV genome detection was possible over the entire sampling period. Soil pH, structure, and ambient temperature played a role in the stability of infectious ASFV. Infectious ASFV was demonstrated in specimens originating from sterile sand for at least three weeks, from beach sand for up to two weeks, from yard soil for one week, and from swamp soil for three days. The virus was not recovered from two acidic forest soils. All risk mitigation experiments with citric acid or calcium hydroxide resulted in complete inactivation. In conclusion, the stability of infectious ASFV is very low in acidic forest soils but rather high in sandy soils. However, given the high variability, treatment of carcass collection points with disinfectants should be considered. Full article
(This article belongs to the Special Issue African Swine Fever Virus Infection)
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18 pages, 2064 KiB  
Article
Systemic Mycobacterium kansasii Infection in Two Related Cats
by Petra Černá, Jordan L. Mitchell, Joanna Lodzinska, Paola Cazzini, Katarina Varjonen and Danièlle A. Gunn-Moore
Pathogens 2020, 9(11), 959; https://doi.org/10.3390/pathogens9110959 - 18 Nov 2020
Cited by 11 | Viewed by 6293
Abstract
Mycobacterial infections are a major concern in veterinary medicine because of the difficulty achieving an etiological diagnosis, the challenges and concerns of treatment, and the potential zoonotic risk. Mycobacterium kansasii, a slow-growing non-tuberculous mycobacteria, causes disease in both humans and animals. While [...] Read more.
Mycobacterial infections are a major concern in veterinary medicine because of the difficulty achieving an etiological diagnosis, the challenges and concerns of treatment, and the potential zoonotic risk. Mycobacterium kansasii, a slow-growing non-tuberculous mycobacteria, causes disease in both humans and animals. While infections have been well described in humans, where it may be misdiagnosed as tuberculosis, there are fewer reports in animals. Only four cases have been reported in the domestic cat. This case report describes systemic M. kansasii infection in two sibling indoor-only cats that presented two and half years apart with cutaneous disease that was found to be associated with osteolytic and pulmonary pathology. Infection with M. kansasii was confirmed in both cats by polymerase chain reaction on fine-needle aspirate of a lumbosacral soft tissue mass in one cat and on a tissue punch biopsy of a skin lesion in the other; interferon-gamma release assay inferred M. avium-complex and M. tuberculosis-complex infection in the two cats, respectively. Both patients made a full recovery following antimicrobial therapy with rifampicin, azithromycin, and pradofloxacin (plus N-acetyl cysteine in cat 2). This report highlights successful treatment of systemic M. kansasii mycobacteriosis in the cat and the challenge of accurately diagnosing this infection. Full article
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34 pages, 2696 KiB  
Review
Critical Review: Propensity of Premise Plumbing Pipe Materials to Enhance or Diminish Growth of Legionella and Other Opportunistic Pathogens
by Abraham C. Cullom, Rebekah L. Martin, Yang Song, Krista Williams, Amanda Williams, Amy Pruden and Marc A. Edwards
Pathogens 2020, 9(11), 957; https://doi.org/10.3390/pathogens9110957 - 17 Nov 2020
Cited by 68 | Viewed by 9616
Abstract
Growth of Legionella pneumophila and other opportunistic pathogens (OPs) in drinking water premise plumbing poses an increasing public health concern. Premise plumbing is constructed of a variety of materials, creating complex environments that vary chemically, microbiologically, spatially, and temporally in a manner likely [...] Read more.
Growth of Legionella pneumophila and other opportunistic pathogens (OPs) in drinking water premise plumbing poses an increasing public health concern. Premise plumbing is constructed of a variety of materials, creating complex environments that vary chemically, microbiologically, spatially, and temporally in a manner likely to influence survival and growth of OPs. Here we systematically review the literature to critically examine the varied effects of common metallic (copper, iron) and plastic (PVC, cross-linked polyethylene (PEX)) pipe materials on factors influencing OP growth in drinking water, including nutrient availability, disinfectant levels, and the composition of the broader microbiome. Plastic pipes can leach organic carbon, but demonstrate a lower disinfectant demand and fewer water chemistry interactions. Iron pipes may provide OPs with nutrients directly or indirectly, exhibiting a high disinfectant demand and potential to form scales with high surface areas suitable for biofilm colonization. While copper pipes are known for their antimicrobial properties, evidence of their efficacy for OP control is inconsistent. Under some circumstances, copper’s interactions with premise plumbing water chemistry and resident microbes can encourage growth of OPs. Plumbing design, configuration, and operation can be manipulated to control such interactions and health outcomes. Influences of pipe materials on OP physiology should also be considered, including the possibility of influencing virulence and antibiotic resistance. In conclusion, all known pipe materials have a potential to either stimulate or inhibit OP growth, depending on the circumstances. This review delineates some of these circumstances and informs future research and guidance towards effective deployment of pipe materials for control of OPs. Full article
(This article belongs to the Special Issue Legionella Contamination in Water Environment)
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23 pages, 1956 KiB  
Review
Porphyromonas gingivalis and Its Systemic Impact: Current Status
by Feng Mei, Mengru Xie, Xiaofei Huang, Yanlin Long, Xiaofeng Lu, Xiaoli Wang and Lili Chen
Pathogens 2020, 9(11), 944; https://doi.org/10.3390/pathogens9110944 - 13 Nov 2020
Cited by 122 | Viewed by 14990
Abstract
The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of [...] Read more.
The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of this organism, the evidence of its connection to systemic diseases has become more apparent over the last decade. A significant amount of research has explored the role of Porphyromonas gingivalis in atherosclerosis, Alzheimer’s disease, rheumatoid arthritis, diabetes, and adverse pregnancy outcomes, while relatively few studies have examined its contribution to respiratory diseases, nonalcoholic fatty liver disease, and depression. Here, we provide an overview of the current state of knowledge about Porphyromonas gingivalis and its systemic impact in an aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which Porphyromonas gingivalis is involved in the onset or exacerbation of diseases, together with its effects on systemic health, are covered. Although a few results remain controversial, it is now evident that Porphyromonas gingivalis should be regarded as a modifiable factor for several diseases. Full article
(This article belongs to the Special Issue Oral Immunology and Periodontitis)
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20 pages, 955 KiB  
Review
Adhesins of Brucella: Their Roles in the Interaction with the Host
by Magalí G. Bialer, Gabriela Sycz, Florencia Muñoz González, Mariana C. Ferrero, Pablo C. Baldi and Angeles Zorreguieta
Pathogens 2020, 9(11), 942; https://doi.org/10.3390/pathogens9110942 - 12 Nov 2020
Cited by 25 | Viewed by 4683
Abstract
A central aspect of Brucella pathogenicity is its ability to invade, survive, and replicate in diverse phagocytic and non-phagocytic cell types, leading to chronic infections and chronic inflammatory phenomena. Adhesion to the target cell is a critical first step in the invasion process. [...] Read more.
A central aspect of Brucella pathogenicity is its ability to invade, survive, and replicate in diverse phagocytic and non-phagocytic cell types, leading to chronic infections and chronic inflammatory phenomena. Adhesion to the target cell is a critical first step in the invasion process. Several Brucella adhesins have been shown to mediate adhesion to cells, extracellular matrix components (ECM), or both. These include the sialic acid-binding proteins SP29 and SP41 (binding to erythrocytes and epithelial cells, respectively), the BigA and BigB proteins that contain an Ig-like domain (binding to cell adhesion molecules in epithelial cells), the monomeric autotransporters BmaA, BmaB, and BmaC (binding to ECM components, epithelial cells, osteoblasts, synoviocytes, and trophoblasts), the trimeric autotransporters BtaE and BtaF (binding to ECM components and epithelial cells) and Bp26 (binding to ECM components). An in vivo role has also been shown for the trimeric autotransporters, as deletion mutants display decreased colonization after oral and/or respiratory infection in mice, and it has also been suggested for BigA and BigB. Several adhesins have shown unipolar localization, suggesting that Brucella would express an adhesive pole. Adhesin-based vaccines may be useful to prevent brucellosis, as intranasal immunization in mice with BtaF conferred high levels of protection against oral challenge with B. suis. Full article
(This article belongs to the Special Issue Host Immune Responses and Pathogenesis to Brucella spp. Infection)
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13 pages, 904 KiB  
Article
Disappearance of TBEV Circulation among Rodents in a Natural Focus in Alsace, Eastern France
by Laure Bournez, Gerald Umhang, Marie Moinet, Jean-Marc Boucher, Jean-Michel Demerson, Christophe Caillot, Léo Legras, Elodie Devillers, Yves Hansmann, Aurélie Velay, Céline Richomme, Sara Moutailler and Franck Boué
Pathogens 2020, 9(11), 930; https://doi.org/10.3390/pathogens9110930 - 10 Nov 2020
Cited by 16 | Viewed by 3382
Abstract
Tick-borne encephalitis virus (TBEV) depends mainly on a fragile mode of transmission, the co-feeding between infected nymphs and larvae on rodents, and thus persists under a limited set of biotic and abiotic conditions. If these conditions change, natural TBEV foci might be unstable [...] Read more.
Tick-borne encephalitis virus (TBEV) depends mainly on a fragile mode of transmission, the co-feeding between infected nymphs and larvae on rodents, and thus persists under a limited set of biotic and abiotic conditions. If these conditions change, natural TBEV foci might be unstable over time. We conducted a longitudinal study over seven years in a mountain forest in Alsace, Eastern France, located at the western border of known TBEV distribution. The objectives were (i) to monitor the persistence of TBEV circulation between small mammals and ticks and (ii) to discuss the presence of TBEV circulation in relation to the synchronous activity of larvae and nymphs, to the densities of questing nymphs and small mammals, and to potential changes in meteorological conditions and deer densities. Small mammals were trapped five times per year from 2012 to 2018 to collect blood samples and record the presence of feeding ticks, and were then released. Questing nymphs were collected twice a year. Overall, 1344 different small mammals (Myodes glareolus and Apodemus flavicollis) were captured and 2031 serum samples were tested for the presence of antibodies against TBEV using an in-house ELISA. Seropositive rodents (2.1%) were only found from 2012 to 2015, suggesting that the virus disappeared afterwards. In parallel, we observed unusual variations in inter-annual nymph abundance and intra-annual larval activity that could be related to exceptional meteorological conditions. Changes in the densities of questing nymphs and deer associated with the natural stochastic variations in the frequency of contacts between rodents and infected ticks may have contributed to the endemic fadeout of TBEV on the study site. Further studies are needed to assess whether such events occur relatively frequently in the area, which could explain the low human incidence of TBE in Alsace and even in other areas of France. Full article
(This article belongs to the Section Animal Pathogens)
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32 pages, 3383 KiB  
Review
Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny
by Sharon Tirosh-Levy, Yuval Gottlieb, Lindsay M. Fry, Donald P. Knowles and Amir Steinman
Pathogens 2020, 9(11), 926; https://doi.org/10.3390/pathogens9110926 - 8 Nov 2020
Cited by 68 | Viewed by 9445
Abstract
Equine piroplasmosis (EP), caused by the hemoparasites Theileria equi, Theileria haneyi, and Babesia caballi, is an important tick-borne disease of equines that is prevalent in most parts of the world. Infection may affect animal welfare and has economic impacts related [...] Read more.
Equine piroplasmosis (EP), caused by the hemoparasites Theileria equi, Theileria haneyi, and Babesia caballi, is an important tick-borne disease of equines that is prevalent in most parts of the world. Infection may affect animal welfare and has economic impacts related to limitations in horse transport between endemic and non-endemic regions, reduced performance of sport horses and treatment costs. Here, we analyzed the epidemiological, serological, and molecular diagnostic data published in the last 20 years, and all DNA sequences submitted to GenBank database, to describe the current global prevalence of these parasites. We demonstrate that EP is endemic in most parts of the world, and that it is spreading into more temperate climates. We emphasize the importance of using DNA sequencing and genotyping to monitor the spread of parasites, and point to the necessity of further studies to improve genotypic characterization of newly recognized parasite species and strains, and their linkage to virulence. Full article
(This article belongs to the Special Issue Animal Parasitic Diseases)
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46 pages, 2051 KiB  
Review
The Destructive Fungal Pathogen Botrytis cinerea—Insights from Genes Studied with Mutant Analysis
by Nicholas Cheung, Lei Tian, Xueru Liu and Xin Li
Pathogens 2020, 9(11), 923; https://doi.org/10.3390/pathogens9110923 - 7 Nov 2020
Cited by 87 | Viewed by 11693
Abstract
Botrytis cinerea is one of the most destructive fungal pathogens affecting numerous plant hosts, including many important crop species. As a molecularly under-studied organism, its genome was only sequenced at the beginning of this century and it was recently updated with improved gene [...] Read more.
Botrytis cinerea is one of the most destructive fungal pathogens affecting numerous plant hosts, including many important crop species. As a molecularly under-studied organism, its genome was only sequenced at the beginning of this century and it was recently updated with improved gene annotation and completeness. In this review, we summarize key molecular studies on B. cinerea developmental and pathogenesis processes, specifically on genes studied comprehensively with mutant analysis. Analyses of these studies have unveiled key genes in the biological processes of this pathogen, including hyphal growth, sclerotial formation, conidiation, pathogenicity and melanization. In addition, our synthesis has uncovered gaps in the present knowledge regarding development and virulence mechanisms. We hope this review will serve to enhance the knowledge of the biological mechanisms behind this notorious fungal pathogen. Full article
(This article belongs to the Collection Reviews for "Plant Pathogens")
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19 pages, 959 KiB  
Review
RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication
by Marta Szabat, Dagny Lorent, Tomasz Czapik, Maria Tomaszewska, Elzbieta Kierzek and Ryszard Kierzek
Pathogens 2020, 9(11), 925; https://doi.org/10.3390/pathogens9110925 - 7 Nov 2020
Cited by 20 | Viewed by 5385
Abstract
Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness [...] Read more.
Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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14 pages, 7650 KiB  
Article
Prevalence, Intensity, and Correlates of Schistosomiasis and Soil-Transmitted Helminth Infections after Five Rounds of Preventive Chemotherapy among School Children in Southern Ethiopia
by Tigist Dires Gebreyesus, Tafesse Tadele, Kalkidan Mekete, Abbie Barry, Habtamu Gashaw, Workagegnehu Degefe, Birkneh Tilahun Tadesse, Heran Gerba, Parthasarathi Gurumurthy, Eyasu Makonnen and Eleni Aklillu
Pathogens 2020, 9(11), 920; https://doi.org/10.3390/pathogens9110920 - 6 Nov 2020
Cited by 26 | Viewed by 4111
Abstract
Preventive chemotherapy (PC) is a WHO-recommended strategy to control and eliminate schistosomiasis and soil-transmitted helminths (STHs). We assessed the prevalence, intensity, and correlates of schistosomiasis and STH infection after five rounds of PC in southern Ethiopia. A total of 3162 school children from [...] Read more.
Preventive chemotherapy (PC) is a WHO-recommended strategy to control and eliminate schistosomiasis and soil-transmitted helminths (STHs). We assessed the prevalence, intensity, and correlates of schistosomiasis and STH infection after five rounds of PC in southern Ethiopia. A total of 3162 school children from four schools in Wondo Gennet and Hawella Tula districts were screened for Schistosoma mansoni and STHs infection. The overall prevalence of S. mansoni infection was 25.8% (range between schools 11.6% to 54.1%), with light (19.1%), moderate (5.3%), and heavy (1.4%) infection intensities. A total of 61.6% S. mansoni-infected children were STH co-infected. The overall prevalence of STHs infection was 54.7% (range between schools 30.6–71.0%), with moderate-to-heavy intensity infections being 16.3%. Ascaris lumbricoides was the most prevalent 45% (95% CI, 43.5–47) followed by Trichuris trichiura 25.3% (95% CI, 23.8–26.9) and hookworm 6.1% (95% CI, 5.3–7). A total of 33.7% of STHs-infected children had A. lumbricoides and T. trichiura co-infections. S. mansoni infection was significantly associated with school and STHs co-infection (p < 0.001). STH infection was correlated with school and younger age (p < 0.001). Despite repeated PC, S. mansoni and STH infection remain significant health problems, and the WHO target to control schistosomiasis and eliminate STH by 2020 may not be achieved. Intensified control and prevention measures, including drug efficacy surveillance, is recommended. Full article
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18 pages, 562 KiB  
Review
Strategies for Assessing Arbovirus Genetic Variability in Vectors and/or Mammals
by Camille Victoire Migné, Sara Moutailler and Houssam Attoui
Pathogens 2020, 9(11), 915; https://doi.org/10.3390/pathogens9110915 - 5 Nov 2020
Cited by 9 | Viewed by 3496
Abstract
Animal arboviruses replicate in their invertebrate vectors and vertebrate hosts. They use several strategies to ensure replication/transmission. Their high mutation rates and propensity to generate recombinants and/or genome segment reassortments help them adapt to new hosts/emerge in new geographical areas. Studying arbovirus genetic [...] Read more.
Animal arboviruses replicate in their invertebrate vectors and vertebrate hosts. They use several strategies to ensure replication/transmission. Their high mutation rates and propensity to generate recombinants and/or genome segment reassortments help them adapt to new hosts/emerge in new geographical areas. Studying arbovirus genetic variability has been used to identify indicators which predict their potential to adapt to new hosts and/or emergence and in particular quasi-species. Multiple studies conducted with insect-borne viruses laid the foundations for the “trade-off” hypothesis (alternation of host transmission cycle constrains arbovirus evolution). It was extrapolated to tick-borne viruses, where too few studies have been conducted, even though humans faced emergence of numerous tick-borne virus during the last decades. There is a paucity of information regarding genetic variability of these viruses. In addition, insects and ticks do not have similar lifecycles/lifestyles. Indeed, tick-borne viruses are longer associated with their vectors due to tick lifespan. The objectives of this review are: (i) to describe the state of the art for all strategies developed to study genetic variability of insect-borne viruses both in vitro and in vivo and potential applications to tick-borne viruses; and (ii) to highlight the specificities of arboviruses and vectors as a complex and diverse system. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Arboviruses)
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18 pages, 1091 KiB  
Review
Antibody-Based Immunotherapeutic Strategies for COVID-19
by Jamal Hussen, Mahmoud Kandeel, Maged Gomaa Hemida and Abdullah I. A. Al-Mubarak
Pathogens 2020, 9(11), 917; https://doi.org/10.3390/pathogens9110917 - 5 Nov 2020
Cited by 15 | Viewed by 4140
Abstract
Global efforts to contain the coronavirus disease-2019 (COVID-19) include the development of novel preventive vaccines and effective therapeutics. Passive antibody therapies using convalescent plasma, SARS-CoV-2 (Severe-Acute-Respiratory-Syndrome-Corona-Virus-2)-specific neutralizing antibodies (NAbs), and the development of monoclonal antibodies (MAbs) are among the most promising strategies for [...] Read more.
Global efforts to contain the coronavirus disease-2019 (COVID-19) include the development of novel preventive vaccines and effective therapeutics. Passive antibody therapies using convalescent plasma, SARS-CoV-2 (Severe-Acute-Respiratory-Syndrome-Corona-Virus-2)-specific neutralizing antibodies (NAbs), and the development of monoclonal antibodies (MAbs) are among the most promising strategies for prophylaxis and treatment of SARS-CoV-2 infections. In addition, several immunomodulatory antibodies acting via several mechanisms to boost the host immune defense against SARS-CoV-2 infection as well as to avoid the harmful overreaction of the immune system are currently under clinical trial. Our main objective is to present the current most up-to-date progress in some clinical trials registered at ClinicalTrials.gov. We highlight the pros and pitfalls of several SARS-CoV-2 antibody-based immunotherapeutics. Full article
(This article belongs to the Collection SARS-CoV Infections)
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14 pages, 252 KiB  
Review
Zika Virus
by Sophie Masmejan, Didier Musso, Manon Vouga, Leo Pomar, Pradip Dashraath, Milos Stojanov, Alice Panchaud and David Baud
Pathogens 2020, 9(11), 898; https://doi.org/10.3390/pathogens9110898 - 28 Oct 2020
Cited by 81 | Viewed by 11888
Abstract
Zika virus (ZIKV), a neurotropic single-stranded RNA flavivirus, remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in populations where ZIKV has adapted to a nexus involving the Aedes mosquitoes and humans. To date, outbreaks of ZIKV have occurred in [...] Read more.
Zika virus (ZIKV), a neurotropic single-stranded RNA flavivirus, remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in populations where ZIKV has adapted to a nexus involving the Aedes mosquitoes and humans. To date, outbreaks of ZIKV have occurred in Africa, Southeast Asia, the Pacific islands, the Americas, and the Caribbean. Emerging evidence, however, suggests that the virus also has the potential to cause infections in Europe, where autochtonous transmission of the virus has been identified. This review focuses on evolving ZIKV epidemiology, modes of transmission and host-virus interactions. The clinical manifestations, diagnostic issues relating to cross-reactivity to the dengue flavivirus and concerns surrounding ZIKV infection in pregnancy are discussed. In the last section, current challenges in treatment and prevention are outlined. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Arboviruses)
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16 pages, 25265 KiB  
Article
Multiple Antigenic Peptide-Based Vaccines Targeting Ixodes ricinus Neuropeptides Induce a Specific Antibody Response but Do Not Impact Tick Infestation
by Consuelo Almazán, Ladislav Šimo, Lisa Fourniol, Sabine Rakotobe, Jérémie Borneres, Martine Cote, Sandy Peltier, Jennifer Mayé, Nicolas Versillé, Jennifer Richardson and Sarah I. Bonnet
Pathogens 2020, 9(11), 900; https://doi.org/10.3390/pathogens9110900 - 28 Oct 2020
Cited by 13 | Viewed by 3577
Abstract
Synthetic peptide vaccines were designed to target the neuropeptides innervating Ixodes ricinus salivary glands and hindgut and they were tested for their capacity to afford protective immunity against nymphs or larvae and Anaplasma phagocytophilum-infected nymph infestation, in mice and sheep, respectively. In [...] Read more.
Synthetic peptide vaccines were designed to target the neuropeptides innervating Ixodes ricinus salivary glands and hindgut and they were tested for their capacity to afford protective immunity against nymphs or larvae and Anaplasma phagocytophilum-infected nymph infestation, in mice and sheep, respectively. In both models, the assembly of SIFamide (SIFa) or myoinhibitory peptide (MIP) neuropeptides into multiple antigenic peptide constructs (MAPs) elicited a robust IgG antibody response following immunization. Nevertheless, no observable detrimental impact on nymphs was evidenced in mice, and, unfortunately, the number of engorged nymphs on sheep was insufficient for firm conclusions to be drawn, including for bacterial transmission. Regarding larvae, while vaccination of the sheep did not globally diminish tick feeding success or development, analyses of animals at the individual level revealed a negative correlation between anti-SIFa and MIP antibody levels and larva-to-nymph molting success for both antigens. Our results provide a proof of principle and precedent for the use of MAPs for the induction of immunity against tick peptide molecules. Although the present study did not provide the expected level of protection, it inaugurates a new strategy for protection against ticks based on the immunological targeting of key components of their nervous system. Full article
(This article belongs to the Collection Advances in Tick Research)
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9 pages, 973 KiB  
Review
Heterotrimeric G-Protein Signalers and RGSs in Aspergillus fumigatus
by Hee-Soo Park, Min-Ju Kim, Jae-Hyuk Yu and Kwang-Soo Shin
Pathogens 2020, 9(11), 902; https://doi.org/10.3390/pathogens9110902 - 28 Oct 2020
Cited by 20 | Viewed by 6345
Abstract
The heterotrimeric G-protein (G-protein) signaling pathway is one of the most important signaling pathways that transmit external signals into the inside of the cell, triggering appropriate biological responses. The external signals are sensed by various G-protein-coupled receptors (GPCRs) and transmitted into G-proteins consisting [...] Read more.
The heterotrimeric G-protein (G-protein) signaling pathway is one of the most important signaling pathways that transmit external signals into the inside of the cell, triggering appropriate biological responses. The external signals are sensed by various G-protein-coupled receptors (GPCRs) and transmitted into G-proteins consisting of the α, β, and γ subunits. Regulators of G-protein signaling (RGSs) are the key controllers of G-protein signaling pathways. GPCRs, G-proteins, and RGSs are the primary upstream components of the G-protein signaling pathway, and they are highly conserved in most filamentous fungi, playing diverse roles in biological processes. Recent studies characterized the G-protein signaling components in the opportunistic pathogenic fungus Aspergillus fumigatus. In this review, we have summarized the characteristics and functions of GPCRs, G-proteins, and RGSs, and their regulatory roles in governing fungal growth, asexual development, germination, stress tolerance, and virulence in A. fumigatus. Full article
(This article belongs to the Special Issue Signal Transduction in Pathogenic Fungi)
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12 pages, 1921 KiB  
Article
Quantitative Risk Assessment for the Introduction of Bovine Leukemia Virus-Infected Cattle Using a Cattle Movement Network Analysis
by Kosuke Notsu, Anuwat Wiratsudakul, Shuya Mitoma, Hala El Daous, Chiho Kaneko, Heba M. El-Khaiat, Junzo Norimine and Satoshi Sekiguchi
Pathogens 2020, 9(11), 903; https://doi.org/10.3390/pathogens9110903 - 28 Oct 2020
Cited by 11 | Viewed by 3201
Abstract
The cattle industry is suffering economic losses caused by bovine leukemia virus (BLV) and enzootic bovine leukosis (EBL), the clinical condition associated with BLV infection. This pathogen spreads easily without detection by farmers and veterinarians due to the lack of obvious clinical signs. [...] Read more.
The cattle industry is suffering economic losses caused by bovine leukemia virus (BLV) and enzootic bovine leukosis (EBL), the clinical condition associated with BLV infection. This pathogen spreads easily without detection by farmers and veterinarians due to the lack of obvious clinical signs. Cattle movement strongly contributes to the inter-farm transmission of BLV. This study quantified the farm-level risk of BLV introduction using a cattle movement analysis. A generalized linear mixed model predicting the proportion of BLV-infected cattle was constructed based on weighted in-degree centrality. Our results suggest a positive association between weighted in-degree centrality and the estimated number of introduced BLV-infected cattle. Remarkably, the introduction of approximately six cattle allowed at least one BLV-infected animal to be added to the farm in the worst-case scenario. These data suggest a high risk of BLV infection on farms with a high number of cattle being introduced. Our findings indicate the need to strengthen BLV control strategies, especially along the chain of cattle movement. Full article
(This article belongs to the Collection Bovine Leukemia Virus Infection)
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15 pages, 1322 KiB  
Review
Dangerous Liaisons: Interactions of Cryptococcus neoformans with Host Phagocytes
by Elizabeth A. Gaylord, Hau Lam Choy and Tamara L. Doering
Pathogens 2020, 9(11), 891; https://doi.org/10.3390/pathogens9110891 - 27 Oct 2020
Cited by 24 | Viewed by 5894
Abstract
Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of death in immunocompromised individuals. The interactions of this yeast with host phagocytes are critical to disease outcome, and C. neoformans is equipped with an array of factors to modulate these processes. [...] Read more.
Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of death in immunocompromised individuals. The interactions of this yeast with host phagocytes are critical to disease outcome, and C. neoformans is equipped with an array of factors to modulate these processes. Cryptococcal infection begins with the deposition of infectious particles into the lungs, where the fungal cells deploy various antiphagocytic factors to resist internalization by host cells. If the cryptococci are still engulfed, they can survive and proliferate within host cells by modulating the phagolysosome environment in which they reside. Lastly, cryptococcal cells may escape from phagocytes by host cell lysis, nonlytic exocytosis, or lateral cell-to-cell transfer. The interactions between C. neoformans and host phagocytes also influence the dissemination of this pathogen to the brain, where it may cross the blood-brain barrier and cause an often-fatal meningoencephalitis. In this review, we highlight key cryptococcal factors involved in various stages of cryptococcal-host interaction and pathogenesis. Full article
(This article belongs to the Special Issue Pathogenesis of Cryptococcus neoformans)
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13 pages, 2293 KiB  
Review
The Attenuated Pseudorabies Virus Vaccine Strain Bartha K61: A Brief Review on the Knowledge Gathered during 60 Years of Research
by Jonas L. Delva, Hans J. Nauwynck, Thomas C. Mettenleiter and Herman W. Favoreel
Pathogens 2020, 9(11), 897; https://doi.org/10.3390/pathogens9110897 - 27 Oct 2020
Cited by 53 | Viewed by 5156
Abstract
Pseudorabies virus (PRV) is a member of the alphaherpesvirus subfamily of the herpesviruses and is the causative agent of Aujeszky’s disease in pigs, causing respiratory, neurological, and reproductive symptoms. Given the heavy economic losses associated with Aujeszky’s disease epidemics, great efforts were made [...] Read more.
Pseudorabies virus (PRV) is a member of the alphaherpesvirus subfamily of the herpesviruses and is the causative agent of Aujeszky’s disease in pigs, causing respiratory, neurological, and reproductive symptoms. Given the heavy economic losses associated with Aujeszky’s disease epidemics, great efforts were made to develop efficacious vaccines. One of the best modified live vaccines to this day is the attenuated Bartha K61 strain. The use of this vaccine in extensive vaccination programs worldwide has assisted considerably in the eradication of PRV from the domesticated pig population in numerous countries. The Bartha K61 strain was described in 1961 by Adorján Bartha in Budapest and was obtained by serial passaging in different cell cultures. Ever since, it has been intensively studied by several research groups, for example, to explore its efficacy as a vaccine strain, to molecularly and mechanistically explain its attenuation, and to use it as a retrograde neuronal tracer and as a vector vaccine. Given that the Bartha K61 vaccine strain celebrates its 60th birthday in 2021 with no sign of retirement, this review provides a short summary of the knowledge on its origin, characteristics, and use as a molecular tool and as a vaccine. Full article
(This article belongs to the Special Issue Pseudorabies Virus Infections)
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10 pages, 898 KiB  
Article
Effectiveness of Chemical Compounds Used against African Swine Fever Virus in Commercial Available Disinfectants
by Małgorzata Juszkiewicz, Marek Walczak, Natalia Mazur-Panasiuk and Grzegorz Woźniakowski
Pathogens 2020, 9(11), 878; https://doi.org/10.3390/pathogens9110878 - 24 Oct 2020
Cited by 45 | Viewed by 8843
Abstract
African swine fever (ASF) causes huge economic losses and is one of most dangerous diseases of pigs. The disease is known for almost 100 years, an effective vaccine or treatment is still unavailable, only proper biosecurity measures, including disinfection, are being applied, in [...] Read more.
African swine fever (ASF) causes huge economic losses and is one of most dangerous diseases of pigs. The disease is known for almost 100 years, an effective vaccine or treatment is still unavailable, only proper biosecurity measures, including disinfection, are being applied, in order to prevent disease outbreaks. Eight active substances, i.e., formaldehyde, sodium hypochlorite, caustic soda, glutaraldehyde, phenol, benzalkonium chloride, potassium peroxymonosulfate and acetic acid, were tested, in order to confirm their effectiveness against African swine fever virus (ASFV). This specific selection was done based on the World Organisation for Animal Health (OIE)’s recommendation and previous disinfectant studies on surfaces. The result of our study shows that most of them inactivate the virus, in recommended concentrations. In order to reduce the cytotoxicity of the four substances, Microspin S-400 HR columns were applied, therefore making it possible to demonstrate four logarithms virus titer reduction. Sodium hypochlorite, glutaraldehyde, caustic soda and potassium peroxymonosulfate showed the best ASFV inactivation rates, achieving titer reductions over 5 logs. Despite microfiltration, the virucidal activity of formaldehyde was not assessable, due to its high cytotoxicity. Our results showed that cleaning is particularly important, because removal of the soiling provides improved effectiveness of the tested chemical compounds. Full article
(This article belongs to the Special Issue African Swine Fever Virus Infection)
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20 pages, 7011 KiB  
Article
Liver Ischemia Reperfusion Injury, Enhanced by Trained Immunity, Is Attenuated in Caspase 1/Caspase 11 Double Gene Knockout Mice
by Alexander M. Fagenson, Keman Xu, Fatma Saaoud, Gayani Nanayakkara, Nirag C. Jhala, Lu Liu, Charles Drummer, Yu Sun, Kwan N. Lau, Antonio Di Carlo, Xiaohua Jiang, Hong Wang, Sunil S. Karhadkar and Xiaofeng Yang
Pathogens 2020, 9(11), 879; https://doi.org/10.3390/pathogens9110879 - 24 Oct 2020
Cited by 43 | Viewed by 4704
Abstract
Ischemia reperfusion injury (IRI) during liver transplantation increases morbidity and contributes to allograft dysfunction. There are no therapeutic strategies to mitigate IRI. We examined a novel hypothesis: caspase 1 and caspase 11 serve as danger-associated molecular pattern (DAMPs) sensors in IRI. By performing [...] Read more.
Ischemia reperfusion injury (IRI) during liver transplantation increases morbidity and contributes to allograft dysfunction. There are no therapeutic strategies to mitigate IRI. We examined a novel hypothesis: caspase 1 and caspase 11 serve as danger-associated molecular pattern (DAMPs) sensors in IRI. By performing microarray analysis and using caspase 1/caspase 11 double-knockout (Casp DKO) mice, we show that the canonical and non-canonical inflammasome regulators are upregulated in mouse liver IRI. Ischemic pre (IPC)- and post-conditioning (IPO) induce upregulation of the canonical and non-canonical inflammasome regulators. Trained immunity (TI) regulators are upregulated in IPC and IPO. Furthermore, caspase 1 is activated during liver IRI, and Casp DKO attenuates liver IRI. Casp DKO maintained normal liver histology via decreased DNA damage. Finally, the decreased TUNEL assay-detected DNA damage is the underlying histopathological and molecular mechanisms of attenuated liver pyroptosis and IRI. In summary, liver IRI induces the upregulation of canonical and non-canonical inflammasomes and TI enzyme pathways. Casp DKO attenuate liver IRI. Development of novel therapeutics targeting caspase 1/caspase 11 and TI may help mitigate injury secondary to IRI. Our findings have provided novel insights on the roles of caspase 1, caspase 11, and inflammasome in sensing IRI derived DAMPs and TI-promoted IRI-induced liver injury. Full article
(This article belongs to the Section Human Pathogens)
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18 pages, 2666 KiB  
Article
Predictive Accuracy of COVID-19 World Health Organization (WHO) Severity Classification and Comparison with a Bayesian-Method-Based Severity Score (EPI-SCORE)
by Christophe de Terwangne, Jabber Laouni, Lionel Jouffe, Jerome R. Lechien, Vincent Bouillon, Sammy Place, Lucio Capulzini, Shahram Machayekhi, Antonia Ceccarelli, Sven Saussez, Antonio Sorgente and on behalf of EPIBASE TEAM
Pathogens 2020, 9(11), 880; https://doi.org/10.3390/pathogens9110880 - 24 Oct 2020
Cited by 36 | Viewed by 6080
Abstract
Objectives: Assess the predictive accuracy of the WHO COVID-19 severity classification on COVID-19 hospitalized patients. The secondary aim was to compare its predictive power with a new prediction model, named COVID-19 EPI-SCORE, based on a Bayesian network analysis. Methods: We retrospectively analyzed a [...] Read more.
Objectives: Assess the predictive accuracy of the WHO COVID-19 severity classification on COVID-19 hospitalized patients. The secondary aim was to compare its predictive power with a new prediction model, named COVID-19 EPI-SCORE, based on a Bayesian network analysis. Methods: We retrospectively analyzed a population of 295 COVID-19 RT-PCR positive patients hospitalized at Epicura Hospital Center, Belgium, admitted between March 1st and April 30th, 2020. Results: Our cohort’s median age was 73 (62–83) years, and the female proportion was 43%. All patients were classified following WHO severity classification at admission. In total, 125 (42.4%) were classified as Moderate, 69 (23.4%) as Severe, and 101 (34.2%) as Critical. Death proportions through these three classes were 11.2%, 33.3%, and 67.3%, respectively, and the proportions of critically ill patients (dead or needed Invasive Mechanical Ventilation) were 11.2%, 34.8%, and 83.2%, respectively. A Bayesian network analysis was used to create a model to analyze predictive accuracy of the WHO severity classification and to create the EPI-SCORE. The six variables that have been automatically selected by our machine learning algorithm were the WHO severity classification, acute kidney injury, age, Lactate Dehydrogenase Levels (LDH), lymphocytes and activated prothrombin time (aPTT). Receiver Operation Characteristic (ROC) curve indexes hereby obtained were 83.8% and 91% for the models based on WHO classification only and our EPI-SCORE, respectively. Conclusions: Our study shows that the WHO severity classification is reliable in predicting a severe outcome among COVID-19 patients. The addition to this classification of a few clinical and laboratory variables as per our COVID-19 EPI-SCORE has demonstrated to significantly increase its accuracy. Full article
(This article belongs to the Collection SARS-CoV Infections)
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18 pages, 664 KiB  
Review
Extracellular DNA (eDNA): Neglected and Potential Sources of Antibiotic Resistant Genes (ARGs) in the Aquatic Environments
by Periyasamy Sivalingam, John Poté and Kandasamy Prabakar
Pathogens 2020, 9(11), 874; https://doi.org/10.3390/pathogens9110874 - 23 Oct 2020
Cited by 51 | Viewed by 6968
Abstract
Over the past decades, the rising antibiotic resistance bacteria (ARB) are continuing to emerge as a global threat due to potential public health risk. Rapidly evolving antibiotic resistance and its persistence in the environment, have underpinned the need for more studies to identify [...] Read more.
Over the past decades, the rising antibiotic resistance bacteria (ARB) are continuing to emerge as a global threat due to potential public health risk. Rapidly evolving antibiotic resistance and its persistence in the environment, have underpinned the need for more studies to identify the possible sources and limit the spread. In this context, not commonly studied and a neglected genetic material called extracellular DNA (eDNA) is gaining increased attention as it can be one of the significant drivers for transmission of extracellular ARGS (eARGs) via horizontal gene transfer (HGT) to competent environmental bacteria and diverse sources of antibiotic-resistance genes (ARGs) in the environment. Consequently, this review highlights the studies that address the environmental occurrence of eDNA and encoding eARGs and its impact on the environmental resistome. In this review, we also brief the recent dedicated technological advancements that are accelerating extraction of eDNA and the efficiency of treatment technologies in reducing eDNA that focuses on environmental antibiotic resistance and potential ecological health risk. Full article
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23 pages, 1175 KiB  
Article
Identifying Candidate Genetic Markers of CDV Cross-Species Pathogenicity in African Lions
by Julie K. Weckworth, Brian W. Davis, Melody E. Roelke-Parker, Rebecca P. Wilkes, Craig Packer, Ernest Eblate, Michael K. Schwartz and L. Scott Mills
Pathogens 2020, 9(11), 872; https://doi.org/10.3390/pathogens9110872 - 23 Oct 2020
Cited by 15 | Viewed by 4324
Abstract
Canine distemper virus (CDV) is a multi-host pathogen with variable clinical outcomes of infection across and within species. We used whole-genome sequencing (WGS) to search for viral markers correlated with clinical distemper in African lions. To identify candidate markers, we first documented single-nucleotide [...] Read more.
Canine distemper virus (CDV) is a multi-host pathogen with variable clinical outcomes of infection across and within species. We used whole-genome sequencing (WGS) to search for viral markers correlated with clinical distemper in African lions. To identify candidate markers, we first documented single-nucleotide polymorphisms (SNPs) differentiating CDV strains associated with different clinical outcomes in lions in East Africa. We then conducted evolutionary analyses on WGS from all global CDV lineages to identify loci subject to selection. SNPs that both differentiated East African strains and were under selection were mapped to a phylogenetic tree representing global CDV diversity to assess if candidate markers correlated with documented outbreaks of clinical distemper in lions (n = 3). Of 54 SNPs differentiating East African strains, ten were under positive or episodic diversifying selection and 20 occurred in the clinical strain despite strong purifying selection at those loci. Candidate markers were in functional domains of the RNP complex (n = 19), the matrix protein (n = 4), on CDV glycoproteins (n = 5), and on the V protein (n = 1). We found mutations at two loci in common between sequences from three CDV outbreaks of clinical distemper in African lions; one in the signaling lymphocytic activation molecule receptor (SLAM)-binding region of the hemagglutinin protein and another in the catalytic center of phosphodiester bond formation on the large polymerase protein. These results suggest convergent evolution at these sites may have a functional role in clinical distemper outbreaks in African lions and uncover potential novel barriers to pathogenicity in this species. Full article
(This article belongs to the Special Issue Canine Distemper Virus Infection)
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24 pages, 1648 KiB  
Article
Characterization of Legionella pneumophila Populations by Multilocus Variable Number of Tandem Repeats (MLVA) Genotyping from Drinking Water and Biofilm in Hospitals from Different Regions of the West Bank
by Ashraf R. Zayed, Marina Pecellin, Alaa Salah, Hanna Alalam, Suha Butmeh, Michael Steinert, Rene Lesnik, Ingrid Brettar, Manfred G. Höfle and Dina M. Bitar
Pathogens 2020, 9(11), 862; https://doi.org/10.3390/pathogens9110862 - 22 Oct 2020
Cited by 11 | Viewed by 4340
Abstract
The West Bank can be considered a high-risk area for Legionnaires’ disease (LD) due to its hot climate, intermittent water supply and roof storage of drinking water. Legionella, mostly L. pneumophila, are responsible for LD, a severe, community-acquired and nosocomial pneumonia. [...] Read more.
The West Bank can be considered a high-risk area for Legionnaires’ disease (LD) due to its hot climate, intermittent water supply and roof storage of drinking water. Legionella, mostly L. pneumophila, are responsible for LD, a severe, community-acquired and nosocomial pneumonia. To date, no extensive assessment of Legionella spp and L. pneumophila using cultivation in combination with molecular approaches in the West Bank has been published. Two years of environmental surveillance of Legionella in water and biofilms in the drinking water distribution systems (DWDS) of eight hospitals was carried out; 180 L. pneumophila strains were isolated, mostly from biofilms in DWDS. Most of the isolates were identified as serogroup (Sg) 1 (60%) and 6 (30%), while a minor fraction comprised Sg 8 and 10. Multilocus Variable number of tandem repeats Analysis using 13 loci (MLVA-8(12)) was applied as a high-resolution genotyping method and compared to the standard Sequence Based Typing (SBT). The isolates were genotyped in 27 MLVA-8(12) genotypes (Gt), comprising four MLVA clonal complexes (VACC 1; 2; 5; 11). The major fraction of isolates constituted Sequence Type (ST)1 and ST461. Most of the MLVA-genotypes were highly diverse and often unique. The MLVA-genotype composition showed substantial regional variability. In general, the applied MLVA-method made it possible to reproducibly genotype the isolates, and was consistent with SBT but showed a higher resolution. The advantage of the higher resolution was most evident for the subdivision of the large strain sets of ST1 and ST461; these STs were shown to be highly pneumonia-relevant in a former study. This shows that the resolution by MLVA is advantageous for back-tracking risk sites and for the avoidance of outbreaks of L. pneumophila. Overall, our results provide important insights into the detailed population structure of L. pneumophila, allowing for better risk assessment for DWDS. Full article
(This article belongs to the Special Issue Legionella Contamination in Water Environment)
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12 pages, 374 KiB  
Review
Control of Cytokines in Latent Cytomegalovirus Infection
by Pearley Chinta, Erica C. Garcia, Kiran Hina Tajuddin, Naomi Akhidenor, Allyson Davis, Lionel Faure and Juliet V. Spencer
Pathogens 2020, 9(10), 858; https://doi.org/10.3390/pathogens9100858 - 21 Oct 2020
Cited by 12 | Viewed by 4702
Abstract
Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny [...] Read more.
Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny virions, occurs in differentiated cell types, while undifferentiated myeloid precursor cells are the primary site of latent infection. The outcome of HCMV infection depends partly on the cell type and differentiation state but is also influenced by the composition of the immune environment. In this review, we discuss the role of early interactions between HCMV and the host immune system, particularly cytokine and chemokine networks, that facilitate the establishment of lifelong latent infection. A better understanding of these cytokine signaling pathways could lead to novel therapeutic targets that might prevent latency or eradicate latently infected cells. Full article
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection and Latency)
16 pages, 3961 KiB  
Article
Influence of Different Light Regimes on the Mycoparasitic Activity and 6-Pentyl-α-pyrone Biosynthesis in Two Strains of Trichoderma atroviride
by Dubraska Moreno-Ruiz, Alessandro Fuchs, Kristina Missbach, Rainer Schuhmacher and Susanne Zeilinger
Pathogens 2020, 9(10), 860; https://doi.org/10.3390/pathogens9100860 - 21 Oct 2020
Cited by 18 | Viewed by 3842
Abstract
The ascomycete Trichoderma atroviride is well known for its mycoparasitic lifestyle. Similar to other organisms, light is an important cue for T. atroviride. However, besides triggering of conidiation, little is known on the physiological responses of T. atroviride to light. In this study, [...] Read more.
The ascomycete Trichoderma atroviride is well known for its mycoparasitic lifestyle. Similar to other organisms, light is an important cue for T. atroviride. However, besides triggering of conidiation, little is known on the physiological responses of T. atroviride to light. In this study, we analyzed how cultivation under different light wavelengths and regimes impacted the behavior of two T. atroviride wild-type strains: IMI206040 and P1. While colony extension of both strains was slightly affected by light, massive differences in their photoconidation responses became evident. T. atroviride P1 colonies conidiated under all conditions tested including growth in complete darkness, while IMI206040 required white, blue or green light to trigger asexual reproduction. Interestingly, deletion of the stress-activated MAP kinase-encoding gene tmk3 abolished the ability of strain P1 to conidiate in red and yellow light as well as in darkness. Furthermore, light-dependent differences in the mycoparasitic activity and in the biosynthesis of the secondary metabolite 6-pentyl-α-pyrone (6-PP) became evident. 6-PP production was highest upon dark incubation, while light, especially exposure to white light as light/dark cycles, had an inhibitory effect on its biosynthesis. We conclude that the response of T. atroviride to light is strain-dependent and impacts differentiation, mycoparasitism, and 6-PP production; hence, this should be considered in experiments testing the mycoparasitic activity of these fungi. Full article
(This article belongs to the Section Plant Pathogens)
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14 pages, 2679 KiB  
Article
Prevalence of Cytauxzoon felis Infection-Carriers in Eastern Kansas Domestic Cats
by Yvonne M. Wikander, Tippawan Anantatat, Qing Kang and Kathryn E. Reif
Pathogens 2020, 9(10), 854; https://doi.org/10.3390/pathogens9100854 - 20 Oct 2020
Cited by 10 | Viewed by 5422
Abstract
Cytauxzoon felis is a hemoprotozoal tick-transmitted pathogen of felids. Felids that survive acute disease often remain infected and serve as reservoirs for subsequent tick transmission to other susceptible felines. States adjacent to Kansas have identified C. felis-domestic cat carriers while statewide awareness [...] Read more.
Cytauxzoon felis is a hemoprotozoal tick-transmitted pathogen of felids. Felids that survive acute disease often remain infected and serve as reservoirs for subsequent tick transmission to other susceptible felines. States adjacent to Kansas have identified C. felis-domestic cat carriers while statewide awareness and concern of cytauxzoonosis have increased. The objective of this study was to determine the prevalence of C. felis-carriers in the eastern Kansas domestic cat population using a sensitive quantitative PCR assay targeting the C. felis Cox3 mitochondrial gene. An overall C. felis infection prevalence of 25.8% was determined for asymptomatic domestic cats in eastern Kansas. Significantly more C. felis-carrier cats were identified in spring and fall, suggesting a seasonal fluctuation of survivors. Additionally, a greater percentage of feral and owned cats were positive for C. felis compared to rescue/rescinded cats. This study demonstrates that C. felis-domestic cat carriers are common among cats that spend at least a portion of time outdoors in eastern Kansas, and that more cats likely survive cytauxzoonosis than expected. Understanding the role of domestic cat carriers of C. felis is essential in developing cytauxzoonosis mitigation strategies, including recommending year-round use of acaricide products for all cats that spend any time outdoors. Full article
(This article belongs to the Section Animal Pathogens)
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21 pages, 984 KiB  
Review
Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health
by Srinivas Reddy Pallerla, Dominik Harms, Reimar Johne, Daniel Todt, Eike Steinmann, Mathias Schemmerer, Jürgen J. Wenzel, Jörg Hofmann, James Wai Kuo Shih, Heiner Wedemeyer, C.-Thomas Bock and Thirumalaisamy P. Velavan
Pathogens 2020, 9(10), 856; https://doi.org/10.3390/pathogens9100856 - 20 Oct 2020
Cited by 78 | Viewed by 8915
Abstract
Infection with hepatitis E virus (HEV) represents the most common source of viral hepatitis globally. Although infecting over 20 million people annually in endemic regions, with major outbreaks described since the 1950s, hepatitis E remains an underestimated disease. This review gives a current [...] Read more.
Infection with hepatitis E virus (HEV) represents the most common source of viral hepatitis globally. Although infecting over 20 million people annually in endemic regions, with major outbreaks described since the 1950s, hepatitis E remains an underestimated disease. This review gives a current view of the global circulation and epidemiology of this emerging virus. The history of HEV, from the first reported enteric non-A non-B hepatitis outbreaks, to the discovery of the viral agent and the molecular characterization of the different human pathogenic genotypes, is discussed. Furthermore, the current state of research regarding the virology of HEV is critically assessed, and the challenges towards prevention and diagnosis, as well as clinical risks of the disease described. Together, these points aim to underline the significant impact of hepatitis E on global health and the need for further in-depth research to better understand the pathophysiology and its role in the complex disease manifestations of HEV infection. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)
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29 pages, 1543 KiB  
Review
Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease
by Sahil Jain, Svetlana F. Khaiboullina and Manoj Baranwal
Pathogens 2020, 9(10), 850; https://doi.org/10.3390/pathogens9100850 - 17 Oct 2020
Cited by 21 | Viewed by 7237
Abstract
Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola [...] Read more.
Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (>32,000 cases) and mortality (>13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed. Full article
(This article belongs to the Special Issue Pathogenesis of Emerging Zoonotic Viral Infections)
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17 pages, 1938 KiB  
Article
Sequencing of Historical Isolates, K-mer Mining and High Serological Cross-Reactivity with Ross River Virus Argue against the Presence of Getah Virus in Australia
by Daniel J. Rawle, Wilson Nguyen, Troy Dumenil, Rhys Parry, David Warrilow, Bing Tang, Thuy T. Le, Andrii Slonchak, Alexander A. Khromykh, Viviana P. Lutzky, Kexin Yan and Andreas Suhrbier
Pathogens 2020, 9(10), 848; https://doi.org/10.3390/pathogens9100848 - 16 Oct 2020
Cited by 15 | Viewed by 4984
Abstract
Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated [...] Read more.
Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated that these viruses were virtually identical to the 1955 GETVMM2021 isolate from Malaysia. K-mer mining of the >40,000 terabases of sequence data in the Sequence Read Archive followed by BLASTn confirmation identified multiple GETV sequences in biosamples from Asia (often as contaminants), but not in biosamples from Australia. In contrast, sequence reads aligning to the Australian Ross River virus (RRV) were readily identified in Australian biosamples. To explore the serological relationship between GETV and other alphaviruses, an adult wild-type mouse model of GETV was established. High levels of cross-reactivity and cross-protection were evident for convalescent sera from mice infected with GETV or RRV, highlighting the difficulties associated with the interpretation of early serosurveys reporting GETV antibodies in Australian cattle and pigs. The evidence that GETV circulates in Australia is thus not compelling. Full article
(This article belongs to the Special Issue Animal Vector-Borne Diseases)
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19 pages, 1660 KiB  
Review
Renibacterium salmoninarum—The Causative Agent of Bacterial Kidney Disease in Salmonid Fish
by Mohammad Reza Delghandi, Mansour El-Matbouli and Simon Menanteau-Ledouble
Pathogens 2020, 9(10), 845; https://doi.org/10.3390/pathogens9100845 - 15 Oct 2020
Cited by 29 | Viewed by 9453
Abstract
Renibacterium salmoninarum is one of the oldest known bacterial pathogens of fish. This Gram-positive bacterium is the causative agent of bacterial kidney disease, a chronic infection that is mostly known to infect salmonid fish at low temperatures. Externally, infected fish can display exophthalmia [...] Read more.
Renibacterium salmoninarum is one of the oldest known bacterial pathogens of fish. This Gram-positive bacterium is the causative agent of bacterial kidney disease, a chronic infection that is mostly known to infect salmonid fish at low temperatures. Externally, infected fish can display exophthalmia as well as blebs on the skin and ulcerations alongside haemorrhages at the base of the fins and alongside the lateral line. Internally, the kidney, heart, spleen and liver can show signs of swelling. Granulomas can be seen on various internal organs, as can haemorrhages, and the organs can be covered with a false membrane. Ascites can also accumulate in the abdominal cavity. The bacterium is generally cultivated on specialized media such as kidney disease medium-1 (KDM-1), KDM-2 and selective kidney disease medium (SKDM), and a diagnostic is performed using molecular tools such as PCRs or real-time quantitative PCRs (RT-qPCRs). Several virulence mechanisms have been identified in R. salmoninarum, in particular the protein p57 that is known to play a role in both agglutination and immunosuppression of the host’s defense mechanisms. Control of the disease is difficult; the presence of asymptomatic carriers complicates the eradication of the disease, as does the ability of the bacterium to gain entrance inside the eggs. Bacterin-killed vaccines have proven to be of doubtful efficacy in controlling the disease, and even more recent application of a virulent environmental relative of R. salmoninarum is of limited efficacy. Treatment by antibiotics such as erythromycin, azithromycin and enrofloxacin can be effective but it is slow and requires prolonged treatment. Moreover, antibiotic-resistant strains have been reported. Despite being known for a long time, there is still much to be discovered about R. salmoninarum, notably regarding its virulence mechanisms and its vaccine potential. Consequently, these gaps in knowledge continue to hinder control of this bacterial disease in aquaculture settings. Full article
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20 pages, 3795 KiB  
Article
Enterococcus faecalis Polymicrobial Interactions Facilitate Biofilm Formation, Antibiotic Recalcitrance, and Persistent Colonization of the Catheterized Urinary Tract
by Jordan R. Gaston, Marissa J. Andersen, Alexandra O. Johnson, Kirsten L. Bair, Christopher M. Sullivan, L. Beryl Guterman, Ashely N. White, Aimee L. Brauer, Brian S. Learman, Ana L. Flores-Mireles and Chelsie E. Armbruster
Pathogens 2020, 9(10), 835; https://doi.org/10.3390/pathogens9100835 - 13 Oct 2020
Cited by 55 | Viewed by 5958
Abstract
Indwelling urinary catheters are common in health care settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, [...] Read more.
Indwelling urinary catheters are common in health care settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, we identified Enterococcus faecalis and Proteus mirabilis as the most prevalent and persistent co-colonizers. Clinical isolates of both species successfully co-colonized in a murine model of CAUTI, and they were observed to co-localize on catheter biofilms during infection. We further demonstrate that P. mirabilis preferentially adheres to E. faecalis during biofilm formation, and that contact-dependent interactions between E. faecalis and P. mirabilis facilitate establishment of a robust biofilm architecture that enhances antimicrobial resistance for both species. E. faecalis may therefore act as a pioneer species on urinary catheters, establishing an ideal surface for persistent colonization by more traditional pathogens such as P. mirabilis. Full article
(This article belongs to the Special Issue Microbial Interactions during Infection)
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26 pages, 7849 KiB  
Article
Effects of Naturally Occurring Mutations in Bovine Leukemia Virus 5′-LTR and Tax Gene on Viral Transcriptional Activity
by Aneta Pluta, Luc Willems, Renée N. Douville and Jacek Kuźmak
Pathogens 2020, 9(10), 836; https://doi.org/10.3390/pathogens9100836 - 13 Oct 2020
Cited by 15 | Viewed by 3623
Abstract
Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis (EBL). The long terminal repeat (LTR) plays an indispensable role in viral gene expression. The BLV Tax protein acts as the main transactivator of LTR-driven transcription of [...] Read more.
Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis (EBL). The long terminal repeat (LTR) plays an indispensable role in viral gene expression. The BLV Tax protein acts as the main transactivator of LTR-driven transcription of BLV viral genes. The aim of this study was to analyze mutations in the BLV LTR region and tax gene to determine their association with transcriptional activity. LTRs were obtained from one hundred and six BLV isolates and analyzed for their genetic variability. Fifteen variants were selected and characterized based on mutations in LTR regulatory elements, and further used for in vitro transcription assays. Reporter vectors containing the luciferase gene under the control of each variant BLV promoter sequence, in addition to variant Tax expression vectors, were constructed. Both types of plasmids were used for cotransfection of HeLa cells and the level of luciferase activity was measured as a proxy of transcriptional activity. Marked differences in LTR promoter activity and Tax transactivation activity were observed amongst BLV variants. These results demonstrate that mutations in both the BLV LTR and tax gene can affect the promoter activity, which may have important consequences on proviral load, viral fitness, and transmissibility in BLV-infected cattle. Full article
(This article belongs to the Collection Bovine Leukemia Virus Infection)
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21 pages, 2179 KiB  
Article
Characterization of Mobile Genetic Elements Using Long-Read Sequencing for Tracking Listeria monocytogenes from Food Processing Environments
by Hee Jin Kwon, Zhao Chen, Peter Evans, Jianghong Meng and Yi Chen
Pathogens 2020, 9(10), 822; https://doi.org/10.3390/pathogens9100822 - 7 Oct 2020
Cited by 15 | Viewed by 3182
Abstract
Recently developed nanopore sequencing technologies offer a unique opportunity to rapidly close the genome and to identify complete sequences of mobile genetic elements (MGEs). In this study, 17 isolates of Listeria monocytogenes (Lm) epidemic clone II (ECII) from seven ready-to-eat meat [...] Read more.
Recently developed nanopore sequencing technologies offer a unique opportunity to rapidly close the genome and to identify complete sequences of mobile genetic elements (MGEs). In this study, 17 isolates of Listeria monocytogenes (Lm) epidemic clone II (ECII) from seven ready-to-eat meat or poultry processing facilities, not known to be associated with outbreaks, were shotgun sequenced, and among them, five isolates were further subjected to long-read sequencing. Additionally, 26 genomes of Lm ECII isolates associated with three listeriosis outbreaks in the U.S. and South Africa were obtained from the National Center for Biotechnology Information (NCBI) database and analyzed to evaluate if MGEs may be used as a high-resolution genetic marker for identifying and sourcing the origin of Lm. The analyses identified four comK prophages in 11 non-outbreak isolates from four facilities and three comK prophages in 20 isolates associated with two outbreaks that occurred in the U.S. In addition, three different plasmids were identified among 10 non-outbreak isolates and 14 outbreak isolates. Each comK prophage and plasmid was conserved among the isolates sharing it. Different prophages from different facilities or outbreaks had significant genetic variations, possibly due to horizontal gene transfer. Phylogenetic analysis showed that isolates from the same facility or the same outbreak always closely clustered. The time of most recent common ancestor of the Lm ECII isolates was estimated to be in March 1816 with the average nucleotide substitution rate of 3.1 × 10−7 substitutions per site per year. This study showed that complete MGE sequences provide a good signal to determine the genetic relatedness of Lm isolates, to identify persistence or repeated contamination that occurred within food processing environment, and to study the evolutionary history among closely related isolates. Full article
(This article belongs to the Special Issue Listeria monocytogenes Pathogenesis)
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25 pages, 4015 KiB  
Review
The Pathogenesis of Tuberculosis–The Koch Phenomenon Reinstated
by Robert L. Hunter
Pathogens 2020, 9(10), 813; https://doi.org/10.3390/pathogens9100813 - 4 Oct 2020
Cited by 49 | Viewed by 12688
Abstract
Research on the pathogenesis of tuberculosis (TB) has been hamstrung for half a century by the paradigm that granulomas are the hallmark of active disease. Human TB, in fact, produces two types of granulomas, neither of which is involved in the development of [...] Read more.
Research on the pathogenesis of tuberculosis (TB) has been hamstrung for half a century by the paradigm that granulomas are the hallmark of active disease. Human TB, in fact, produces two types of granulomas, neither of which is involved in the development of adult type or post-primary TB. This disease begins as the early lesion; a prolonged subclinical stockpiling of secreted mycobacterial antigens in foamy alveolar macrophages and nearby highly sensitized T cells in preparation for a massive necrotizing hypersensitivity reaction, the Koch Phenomenon, that produces caseous pneumonia that is either coughed out to form cavities or retained to become the focus of post-primary granulomas and fibrocaseous disease. Post-primary TB progresses if the antigens are continuously released and regresses when they are depleted. This revised paradigm is supported by nearly 200 years of research and suggests new approaches and animal models to investigate long standing mysteries of human TB and vaccines that inhibit the early lesion to finally end its transmission. Full article
(This article belongs to the Special Issue Pathogenesis of Tuberculosis: Challenges and Opportunities)
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24 pages, 1232 KiB  
Review
One Health Approach to Leishmaniases: Understanding the Disease Dynamics through Diagnostic Tools
by Ahyun Hong, Ricardo Andrade Zampieri, Jeffrey Jon Shaw, Lucile Maria Floeter-Winter and Maria Fernanda Laranjeira-Silva
Pathogens 2020, 9(10), 809; https://doi.org/10.3390/pathogens9100809 - 1 Oct 2020
Cited by 51 | Viewed by 8645
Abstract
Leishmaniases are zoonotic vector-borne diseases caused by protozoan parasites of the genus Leishmania that affect millions of people around the globe. There are various clinical manifestations, ranging from self-healing cutaneous lesions to potentially fatal visceral leishmaniasis, all of which are associated with different [...] Read more.
Leishmaniases are zoonotic vector-borne diseases caused by protozoan parasites of the genus Leishmania that affect millions of people around the globe. There are various clinical manifestations, ranging from self-healing cutaneous lesions to potentially fatal visceral leishmaniasis, all of which are associated with different Leishmania species. Transmission of these parasites is complex due to the varying ecological relationships between human and/or animal reservoir hosts, parasites, and sand fly vectors. Moreover, vector-borne diseases like leishmaniases are intricately linked to environmental changes and socioeconomic risk factors, advocating the importance of the One Health approach to control these diseases. The development of an accurate, fast, and cost-effective diagnostic tool for leishmaniases is a priority, and the implementation of various control measures such as animal sentinel surveillance systems is needed to better detect, prevent, and respond to the (re-)emergence of leishmaniases. Full article
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17 pages, 1732 KiB  
Article
Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice
by Markus M. Heimesaat, Soraya Mousavi, Sigri Kløve, Claudia Genger, Dennis Weschka, Andrea Tamas, Dora Reglodi and Stefan Bereswill
Pathogens 2020, 9(10), 805; https://doi.org/10.3390/pathogens9100805 - 30 Sep 2020
Cited by 12 | Viewed by 2672
Abstract
Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the [...] Read more.
Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae. Full article
(This article belongs to the Special Issue Campylobacter Infections)
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12 pages, 2095 KiB  
Article
A Siderophore Analog of Fimsbactin from Acinetobacter Hinders Growth of the Phytopathogen Pseudomonas syringae and Induces Systemic Priming of Immunity in Arabidopsis thaliana
by Fabrice Betoudji, Taha Abd El Rahman, Marvin J. Miller, Manuka Ghosh, Mario Jacques, Kamal Bouarab and François Malouin
Pathogens 2020, 9(10), 806; https://doi.org/10.3390/pathogens9100806 - 30 Sep 2020
Cited by 15 | Viewed by 3652
Abstract
Siderophores produced in soil by plant growth-promoting rhizobacteria (PGPRs) play several roles, including nutrient mobilizers and can be useful as plants defense elicitors. We investigated the role of a synthetic mixed ligand bis-catechol-mono-hydroxamate siderophore (SID) that mimics the chemical structure of a natural [...] Read more.
Siderophores produced in soil by plant growth-promoting rhizobacteria (PGPRs) play several roles, including nutrient mobilizers and can be useful as plants defense elicitors. We investigated the role of a synthetic mixed ligand bis-catechol-mono-hydroxamate siderophore (SID) that mimics the chemical structure of a natural siderophore, fimsbactin, produced by Acinetobacter spp. in the resistance against the phytopathogen Pseudomonas syringaepv tomato DC3000 (Pst DC3000), in Arabidopsis thaliana. We first tested the antibacterial activity of SID against Pst DC3000 in vitro. After confirming that SID had antibacterial activity against Pst DC3000, we tested whether the observed in vitro activity could translate into resistance of Arabidopsis to Pst DC3000, using bacterial loads as endpoints in a plant infection model. Furthermore, using quantitative polymerase chain reaction, we explored the molecular actors involved in the resistance of Arabidopsis induced by SID. Finally, to assure that SID would not interfere with PGPRs, we tested in vitro the influence of SID on the growth of a reference PGPR, Bacillus subtilis. We report here that SID is an antibacterial agent as well as an inducer of systemic priming of resistance in A. thaliana against Pst DC3000, and that SID can, at the same time, promote growth of a PGPR. Full article
(This article belongs to the Special Issue Biological Control of Phytopathogens: Mechanisms and Applications)
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20 pages, 3309 KiB  
Article
Transcriptome Response of Atlantic Salmon (Salmo salar) to a New Piscine Orthomyxovirus
by Francisca Samsing, Pamela Alexandre, Megan Rigby, Richard S. Taylor, Roger Chong and James W. Wynne
Pathogens 2020, 9(10), 807; https://doi.org/10.3390/pathogens9100807 - 30 Sep 2020
Cited by 18 | Viewed by 4196
Abstract
Pilchard orthomyxovirus (POMV) is an emerging pathogen of concern to the salmon industry in Australia. To explore the molecular events that underpin POMV infection, we challenged Atlantic salmon (Salmo salar) post-smolts in seawater via cohabitation. Tissue samples of the head kidney [...] Read more.
Pilchard orthomyxovirus (POMV) is an emerging pathogen of concern to the salmon industry in Australia. To explore the molecular events that underpin POMV infection, we challenged Atlantic salmon (Salmo salar) post-smolts in seawater via cohabitation. Tissue samples of the head kidney and liver were collected from moribund and surviving individuals and analyzed using transcriptome sequencing. Viral loads were higher in the head kidney compared to the liver, yet the liver presented more upregulated genes. Fish infected with POMV showed a strong innate immune response that included the upregulation of pathogen recognition receptors such as RIG-I and Toll-like receptors as well as the induction of interferon-stimulated genes (MX, ISG15). Moribund fish also presented a dramatic induction of pro-inflammatory cytokines, contributing to severe tissue damage and morbidity. An induction of major histocompatibility complex (MHC) class I genes (B2M) and markers of T cell-mediated immunity (CD8-alpha, CD8-beta, Perforin-1, Granzyme-A) was observed in both moribund fish and survivors. In addition, differential connectivity analysis showed that three key regulators (RELA/p65, PRDM1, and HLF) related to cell-mediated immunity had significant differences in connectivity in “clinically healthy” versus “clinically affected” or moribund fish. Collectively, our results show that T cell-mediated immunity plays a central role in the response of Atlantic salmon to the infection with POMV. Full article
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11 pages, 1514 KiB  
Article
Development and Optimization of In-house ELISA for Detection of Human IgG Antibody to SARS-CoV-2 Full Length Spike Protein
by Thamir A. Alandijany, Sherif A. El-Kafrawy, Ahmed M. Tolah, Sayed S. Sohrab, Arwa A. Faizo, Ahmed M. Hassan, Tagreed L. Alsubhi, Norah A. Othman and Esam I. Azhar
Pathogens 2020, 9(10), 803; https://doi.org/10.3390/pathogens9100803 - 28 Sep 2020
Cited by 29 | Viewed by 9287
Abstract
The ongoing coronavirus disease 19 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a threat to human health. Despite this, many affected countries are now in the process of gradual lifting of COVID-19 restrictions that were initially [...] Read more.
The ongoing coronavirus disease 19 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a threat to human health. Despite this, many affected countries are now in the process of gradual lifting of COVID-19 restrictions that were initially implemented in response to the pandemic. The success of the so-called “exit strategy” requires continued surveillance of virus circulation in the community and evaluation of the prevalence of protective immunity among population. Serology tests are valuable tools for these purposes. Herein, SARS-CoV-2 full-length spike (S) recombinant protein was utilized to develop and optimize an indirect enzyme-linked immunoassay (ELISA) that enables a reliable detection of virus-specific IgG antibody in human sera. Importantly, the performance of this assay was evaluated utilizing micro-neutralization (MN) assay as a reference test. Our developed ELISA offers 100% sensitivity, 98.4% specificity, 98.8% agreement, and high overall accuracy. Moreover, the optical density (OD) values of positive samples significantly correlated with their MN titers. The assay specifically detects human IgG antibodies directed against SARS-CoV-2, but not those to Middle East respiratory syndrome coronavirus (MERS-CoV) or human coronavirus HKU1 (HCoV-HKU1). The availability of this in-house ELISA protocol would be valuable for various diagnostic and epidemiological applications. Full article
(This article belongs to the Special Issue COVID-19 in Low and Middle Income Countries)
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17 pages, 3246 KiB  
Article
Species Detection within the Echinococcus granulosus sensu lato Complex by Novel Probe-Based Real-Time PCRs
by Pavlo Maksimov, Hannes Bergmann, Marion Wassermann, Thomas Romig, Bruno Gottstein, Adriano Casulli and Franz J. Conraths
Pathogens 2020, 9(10), 791; https://doi.org/10.3390/pathogens9100791 - 26 Sep 2020
Cited by 27 | Viewed by 4346
Abstract
Infections with eggs of Echinococcus granulosus sensu lato (s.l.) can cause cystic echinococcosis in intermediate host animals and humans. Upon ingestion of viable eggs, oncospheres hatch from the eggs and subsequently develop into fluid-filled larval cysts, most frequently in the liver [...] Read more.
Infections with eggs of Echinococcus granulosus sensu lato (s.l.) can cause cystic echinococcosis in intermediate host animals and humans. Upon ingestion of viable eggs, oncospheres hatch from the eggs and subsequently develop into fluid-filled larval cysts, most frequently in the liver or the lungs. The slowly growing cysts progressively interfere with organ function. The risk of infection is determined by the host range of the parasite, its pathogenicity and other epidemiologically relevant parameters, which differ significantly among the five species within the E. granulosus s.l. complex. It is therefore essential to diagnose the correct species within E. granulosus s.l. to help understand specific disease epidemiology and to facilitate effective implementation of control measures. For this purpose, simple, fast and cost-effective typing techniques are needed. We developed quantitative real-time polymerase chain reactions (qPCRs) to target polymorphic regions in the mitochondrial genome of E. granulosus s.l. In a single-step typing approach, we distinguished E. granulosus s.l. members in four epidemiologically relevant subgroups. These were E. granulosus sensu stricto, E. equinus, E. ortleppi and the E. canadensis cluster. The technique also allowed identification and differentiation of these species from other Echinococcus or Taenia taxa for samples isolated from cysts or faeces. Full article
(This article belongs to the Special Issue Echinococcus)
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14 pages, 4757 KiB  
Article
Inhibition of Mixed Biofilms of Candida albicans and Methicillin-Resistant Staphylococcus aureus by Positively Charged Silver Nanoparticles and Functionalized Silicone Elastomers
by Humberto H. Lara and Jose L. Lopez-Ribot
Pathogens 2020, 9(10), 784; https://doi.org/10.3390/pathogens9100784 - 25 Sep 2020
Cited by 31 | Viewed by 4078
Abstract
Both bacterial and fungal organisms display the ability to form biofilms; however, mixed bacterial/fungal biofilms are particularly difficult to control and eradicate. The opportunistic microbial pathogens Candida albicans and Staphylococcus aureus are among the most frequent causative agents of healthcare-acquired infections, and are [...] Read more.
Both bacterial and fungal organisms display the ability to form biofilms; however, mixed bacterial/fungal biofilms are particularly difficult to control and eradicate. The opportunistic microbial pathogens Candida albicans and Staphylococcus aureus are among the most frequent causative agents of healthcare-acquired infections, and are often co-isolated forming mixed biofilms, especially from contaminated catheters. These mixed species biofilms display a high level of antibiotic resistance; thus, these infections are challenging to treat resulting in excess morbidity and mortality. In the absence of effective conventional antibiotic treatments, nanotechnology-based approaches represent a promising alternative for the treatment of highly recalcitrant polymicrobial biofilm infections. Our group has previously reported on the activity of pure positively charged silver nanoparticles synthesized by a novel microwave technique against single-species biofilms of C. albicans and S. aureus. Here, we have expanded our observations to demonstrate that that silver nanoparticles display dose-dependent activity against dual-species C. albicans/S. aureus biofilms. Moreover, the same nanoparticles were used to functionalize catheter materials, leading to the effective inhibition of the mixed fungal/bacterial biofilms. Overall, our results indicate the potent activity of silver nanoparticles against these cross-kingdom biofilms. More studies are warranted to examine the ability of functionalized catheters in the prevention of catheter-related bloodstream infections. Full article
(This article belongs to the Special Issue Microbial Interactions during Infection)
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14 pages, 241 KiB  
Review
Endothelial Cell Contributions to COVID-19
by Alexandra E. Oxford, Fabio Halla, Evan B. Robertson and Brad E. Morrison
Pathogens 2020, 9(10), 785; https://doi.org/10.3390/pathogens9100785 - 25 Sep 2020
Cited by 17 | Viewed by 4157
Abstract
Understanding of the clinical, histological and molecular features of the novel coronavirus 2019 (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has remained elusive. Coronavirus disease 2019 (COVID-19) caused by this virus has unusual clinical presentation with regard to other related coronaviruses. Recent reports [...] Read more.
Understanding of the clinical, histological and molecular features of the novel coronavirus 2019 (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has remained elusive. Coronavirus disease 2019 (COVID-19) caused by this virus has unusual clinical presentation with regard to other related coronaviruses. Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. Likewise, mounting evidence associates vascular and endothelial cell dysfunction with increased mortality. This review focuses on understanding how endothelial cell pathology is caused by SARS-CoV-2 at the molecular and cellular levels and how these events relate to COVID-19. A detailed examination of current knowledge regarding canonical inflammatory reaction pathways as well as alteration of endothelial cell-derived exosomes and transdifferentiation by SARS-CoV-2 is included in this assessment. Additionally, given an understanding of endothelial contributions to COVID-19, potential therapeutic aims are discussed, particularly as would affect endothelial function and pathology. Full article
(This article belongs to the Section Human Pathogens)
17 pages, 1570 KiB  
Review
Infectious Bronchitis Coronavirus Infection in Chickens: Multiple System Disease with Immune Suppression
by Shahnas M. Najimudeen, Mohamed S. H. Hassan, Susan C. Cork and Mohamed Faizal Abdul-Careem
Pathogens 2020, 9(10), 779; https://doi.org/10.3390/pathogens9100779 - 24 Sep 2020
Cited by 45 | Viewed by 10066
Abstract
In the early 1930s, infectious bronchitis (IB) was first characterized as a respiratory disease in young chickens; later, the disease was also described in older chickens. The etiology of IB was confirmed later as being due to a coronavirus: the infectious bronchitis virus [...] Read more.
In the early 1930s, infectious bronchitis (IB) was first characterized as a respiratory disease in young chickens; later, the disease was also described in older chickens. The etiology of IB was confirmed later as being due to a coronavirus: the infectious bronchitis virus (IBV). Being a coronavirus, IBV is subject to constant genome change due to mutation and recombination, with the consequence of changing clinical and pathological manifestations. The potential use of live attenuated vaccines for the control of IBV infection was demonstrated in the early 1950s, but vaccine breaks occurred due to the emergence of new IBV serotypes. Over the years, various IBV genotypes associated with reproductive, renal, gastrointestinal, muscular and immunosuppressive manifestations have emerged. IBV causes considerable economic impacts on global poultry production due to its pathogenesis involving multiple body systems and immune suppression; hence, there is a need to better understand the pathogenesis of infection and the immune response in order to help developing better management strategies. The evolution of new strains of IBV during the last nine decades against vaccine-induced immune response and changing clinical and pathological manifestations emphasize the necessity of the rational development of intervention strategies based on a thorough understanding of IBV interaction with the host. Full article
(This article belongs to the Special Issue Reviews From Section "Animal Pathogens")
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12 pages, 1242 KiB  
Article
Occurrence of Fungi in the Potable Water of Hospitals: A Public Health Threat
by Giuseppina Caggiano, Giusy Diella, Francesco Triggiano, Nicola Bartolomeo, Francesca Apollonio, Carmen Campanale, Marco Lopuzzo and Maria Teresa Montagna
Pathogens 2020, 9(10), 783; https://doi.org/10.3390/pathogens9100783 - 24 Sep 2020
Cited by 18 | Viewed by 3535
Abstract
Since the last decade, attention towards the occurrence of fungi in potable water has increased. Commensal and saprophytic microorganisms widely distributed in nature are also responsible for causing public health problems. Fungi can contaminate hospital environments, surviving and proliferating in moist and unsterile [...] Read more.
Since the last decade, attention towards the occurrence of fungi in potable water has increased. Commensal and saprophytic microorganisms widely distributed in nature are also responsible for causing public health problems. Fungi can contaminate hospital environments, surviving and proliferating in moist and unsterile conditions. According to Italian regulations, the absence of fungi is not a mandatory parameter to define potable water, as a threshold value for the fungal occurrence has not been defined. This study evaluated the occurrence of fungi in potable water distribution systems in hospitals. The frequency of samples positive for the presence of fungi was 56.9%; among them, filamentous fungi and yeasts were isolated from 94.2% and 9.2% of the samples, respectively. The intensive care unit (87.1%) had the highest frequency of positive samples. Multivariable model (p < 0.0001), the variables of the period of the year (p < 0.0001) and type of department (p = 0.0002) were found to be statistically significant, suggesting a high distribution of filamentous fungi in the potable water of hospitals. Further studies are necessary to validate these results and identify the threshold values of fungi levels for different types of water used for various purposes to ensure the water is safe for consumption and protect public health. Full article
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20 pages, 2911 KiB  
Review
Orthohantaviruses, Emerging Zoonotic Pathogens
by Emmanuel Kabwe, Yuriy Davidyuk, Anton Shamsutdinov, Ekaterina Garanina, Ekaterina Martynova, Kristina Kitaeva, Moffat Malisheni, Guzel Isaeva, Tatiana Savitskaya, Richard A. Urbanowicz, Sergey Morzunov, Cyprian Katongo, Albert Rizvanov and Svetlana Khaiboullina
Pathogens 2020, 9(9), 775; https://doi.org/10.3390/pathogens9090775 - 22 Sep 2020
Cited by 35 | Viewed by 7388
Abstract
Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia [...] Read more.
Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease’s severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates. Full article
(This article belongs to the Special Issue Hemorrhagic Fever Viruses)
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