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Pathogens, Volume 9, Issue 5 (May 2020) – 95 articles

Cover Story (view full-size image): Neogi et al. used a combination of bioinformatics and computer-aided drug design and identified four potential nucleoside inhibitors for the treatment of COVID-19: Remdesivir, 5-Fluorouracil, Ribavirin, and Favipiravir. New clinical trials are supporting their results. View this paper
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12 pages, 2595 KiB  
Article
Cellular Metabolic Profiling of CrFK Cells Infected with Feline Infectious Peritonitis Virus Using Phenotype Microarrays
by Shing Wei Ng, Gayathri Thevi Selvarajah, Yoke Kqueen Cheah, Farina Mustaffa Kamal and Abdul Rahman Omar
Pathogens 2020, 9(5), 412; https://doi.org/10.3390/pathogens9050412 - 25 May 2020
Cited by 4 | Viewed by 3565
Abstract
Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level [...] Read more.
Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis. Methods: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells. Results: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells. Conclusion: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection. Full article
(This article belongs to the Special Issue Feline Infectious Peritonitis)
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11 pages, 1093 KiB  
Article
Wide Range of the Prevalence and Viral Loads of Porcine Circovirus Type 3 (PCV3) in Different Clinical Materials from 21 Polish Pig Farms
by Aleksandra Woźniak, Dagmara Miłek and Tomasz Stadejek
Pathogens 2020, 9(5), 411; https://doi.org/10.3390/pathogens9050411 - 25 May 2020
Cited by 11 | Viewed by 2719
Abstract
Porcine circovirus type 3 (PCV3) was described in different clinical cases and healthy pigs. However, little is known about its circulation in pig farms. In order to assess PCV3 prevalence in 21 Polish farms, serum, feces, and oral fluid samples were examined by [...] Read more.
Porcine circovirus type 3 (PCV3) was described in different clinical cases and healthy pigs. However, little is known about its circulation in pig farms. In order to assess PCV3 prevalence in 21 Polish farms, serum, feces, and oral fluid samples were examined by quantitative real-time PCR. In total, 1451 pairs of serum and feces from the same animals, as well as 327 samples of oral fluids were analyzed. The results showed that PCV3 is more commonly detected in oral fluids (37.3% positives) than in serum (9.7% positives) or feces (15.0% positives) samples. The viral loads detected in these materials ranged from 102.5–107.2 genome equivalent copies/mL. Although in most farms PCV3 was detected post weaning, in nine farms, the virus was also found in groups of suckling piglets, and in six of them viremia was detected. In four farms with reproductive failure, fetal materials were also obtained. PCV3 was detected in 36.0% of fetuses or stillborn piglets (9/25) with viral loads of 103.1–1010.4 genome equivalent copies/mL. In summary, the virus circulation may show different patterns, and congenital or early infection is not uncommon. Precise quantification of PCV3 loads in clinical materials seems to be necessary for the study and diagnosis of the infection. Full article
(This article belongs to the Special Issue Porcine Circovirus Infections)
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15 pages, 2874 KiB  
Article
Evaluation of the Immunomodulatory Ability of Lactic Acid Bacteria Isolated from Feedlot Cattle Against Mastitis Using a Bovine Mammary Epithelial Cells In Vitro Assay
by Kohtaro Fukuyama, Md. Aminul Islam, Michihiro Takagi, Wakako Ikeda-Ohtsubo, Shoichiro Kurata, Hisashi Aso, Graciela Vignolo, Julio Villena and Haruki Kitazawa
Pathogens 2020, 9(5), 410; https://doi.org/10.3390/pathogens9050410 - 25 May 2020
Cited by 18 | Viewed by 4014
Abstract
Bovine mastitis, the inflammation of the mammary gland, affects the quality and quantity of milk yield. Mastitis control relies on single or multiple combinations of antibiotic therapy. Due to increasing antibiotic resistance in pathogens, the intramammary infusion of lactic acid bacteria (LAB) has [...] Read more.
Bovine mastitis, the inflammation of the mammary gland, affects the quality and quantity of milk yield. Mastitis control relies on single or multiple combinations of antibiotic therapy. Due to increasing antibiotic resistance in pathogens, the intramammary infusion of lactic acid bacteria (LAB) has been considered as a potential alternative to antibiotics for treating and preventing bovine mastitis through the improvement of the host immunity. Probiotic effects are a strain-dependent characteristic; therefore, candidate LAB strains have to be evaluated efficiently to find out the ones with the best potential. Here, we investigated LAB strains originally isolated from feedlot cattle’s environment regarding their ability in inducing the Toll-like receptor (TLR)-triggered inflammatory responses in bovine mammary epithelial (BME) cells in vitro. The BME cells were pre-stimulated with the LAB strains individually for 12, 24, and 48 h and then challenged with Escherichia coli-derived lipopolysaccharide (LPS) for 12 h. The mRNA expression of selected immune genes—interleukin 1 alpha (IL-1α), IL-1β, monocyte chemotactic protein 1 (MCP-1), IL-8, chemokine (C-X-C motif) ligand 2 (CXCL2), and CXCL3 were quantified by real-time quantitative PCR (RT-qPCR). Results indicated that pretreatment with some Lactobacillus strains were able to differentially regulate the LPS inflammatory response in BME cells; however, strain-dependent differences were found. The most remarkable effects were found for Lactobacillus acidophilus CRL2074, which reduced the expression of IL-1α, IL-1β, MCP-1, IL-8, and CXCL3, whereas Lactobacillus rhamnosus CRL2084 diminished IL-1β, MCP-1, and IL-8 expression. The pre-stimulation of BME cells with the CRL2074 strain resulted in the upregulated expression of three negative regulators of the TLRs, including the ubiquitin-editing enzyme A20 (also called tumor necrosis factor alpha-induced protein 3, TNFAIP3), single immunoglobin IL-1 single receptor (SIGIRR), and Toll interacting protein (Tollip) after the LPS challenge. The CRL2084 pre-stimulation upregulated only Tollip expression. Our results demonstrated that the L. acidophilus CRL2074 strain possess remarkable immunomodulatory abilities against LPS-induced inflammation in BME cells. This Lactobacillus strain could be used as candidate for in vivo testing due to its beneficial effects in bovine mastitis through intramammary infusion. Our findings also suggest that the BME cells immunoassay system could be of value for the in vitro evaluation of the immunomodulatory abilities of LAB against the inflammation resulting from the intramammary infection with mastitis-related pathogens. Full article
(This article belongs to the Collection Mastitis in Dairy Ruminants)
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8 pages, 447 KiB  
Communication
An Optimized Most Probable Number (MPN) Method to Assess the Number of Thermophilic Free-Living Amoebae (FLA) in Water Samples
by Mirna Moussa, Isabel Marcelino, Vincent Richard, Jérôme Guerlotté and Antoine Talarmin
Pathogens 2020, 9(5), 409; https://doi.org/10.3390/pathogens9050409 - 24 May 2020
Cited by 3 | Viewed by 4351
Abstract
Detection and quantification of pathogenic free-living amoebae (FLA) in water samples is critical for assessing water quality and for disease management issues. The most probable number (MPN) is commonly used to account for FLA in water. Nevertheless, this requires a high number of [...] Read more.
Detection and quantification of pathogenic free-living amoebae (FLA) in water samples is critical for assessing water quality and for disease management issues. The most probable number (MPN) is commonly used to account for FLA in water. Nevertheless, this requires a high number of water replicates and working volumes, and a consequent number of non-nutrient agar (NNA)-plates seeded with Escherichia coli. Herein, we aimed at optimizing this difficult method, taking also into account key factors such as (i) the counting method, (ii) the delay between sample collection and sample processing, and (iii) the temperature during water sample transportation. To simplify the MPN method, we filtrated 1 × 1000 and 1 × 100 mL water samples, and cellulose acetate filters were cut in 10 parts and inverted on NNA-plates overlaid with E. coli. The comparison between the classical and our optimized MPN method showed that the final counts were similar, therefore validating the use of the optimized method. Our results also showed that for thermophilic FLA (such as Naegleria fowleri), water samples can be kept at around +30°C and processed within 24 h. This improved MPN method is now routinely used in our laboratory to control Naegleria sp. in the water samples in Guadeloupe. Full article
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9 pages, 228 KiB  
Review
Role of Hydrogen Peroxide Vapor (HPV) for the Disinfection of Hospital Surfaces Contaminated by Multiresistant Bacteria
by Michele Totaro, Beatrice Casini, Sara Profeti, Benedetta Tuvo, Gaetano Privitera and Angelo Baggiani
Pathogens 2020, 9(5), 408; https://doi.org/10.3390/pathogens9050408 - 24 May 2020
Cited by 18 | Viewed by 5451
Abstract
The emergence of multiresistant bacterial strains as agents of healthcare-related infection in hospitals has prompted a review of the control techniques, with an added emphasis on preventive measures, namely good clinical practices, antimicrobial stewardship, and appropriate environmental cleaning. The latter item is about [...] Read more.
The emergence of multiresistant bacterial strains as agents of healthcare-related infection in hospitals has prompted a review of the control techniques, with an added emphasis on preventive measures, namely good clinical practices, antimicrobial stewardship, and appropriate environmental cleaning. The latter item is about the choice of an appropriate disinfectant as a critical role due to the difficulties often encountered in obtaining a complete eradication of environmental contaminations and reservoirs of pathogens. The present review is focused on the effectiveness of hydrogen peroxide vapor, among the new environmental disinfectants that have been adopted. The method is based on a critical review of the available literature on this topic Full article
(This article belongs to the Section Waterborne/Foodborne/Airborne Pathogens)
11 pages, 1896 KiB  
Article
Analysis of the Leukocyte Response in Calves Suffered from Mycoplasma bovis Pneumonia
by Katarzyna Dudek, Dariusz Bednarek, Urszula Lisiecka, Anna Kycko, Michał Reichert, Krzysztof Kostro and Stanisław Winiarczyk
Pathogens 2020, 9(5), 407; https://doi.org/10.3390/pathogens9050407 - 24 May 2020
Cited by 9 | Viewed by 2692
Abstract
Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis [...] Read more.
Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis (M. bovis) on leukocytes have been performed, but it is difficult to apply these results to in vivo conditions. Additionally, only a few studies on a local immune response in M. bovis pneumonia have been undertaken. In this study, the experimental calf-infection model was used to determine the effect of field M. bovis strains on changes of the peripheral blood leukocyte response, including phagocytic activity and oxygen metabolism by cytometry analyses. An additional aim was to evaluate the lung local immunity of the experimentally infected calves using immunohistochemical staining. The general stimulation of phagocytic and killing activity of peripheral blood leukocytes in response to the M. bovis infection points to upregulation of cellular antimicrobial mechanisms. The local immune response in the infected lungs was characterized by the T- and B-cell stimulation, however, most seen in the increased T lymphocyte response. Post-infection, strong expression of the antigen-presenting cells and phagocytes also confirmed the activation of lung local immunity. In this study—despite the stimulation—both the peripheral and local cellular antimicrobial mechanisms seem to appear ineffective in eliminating M. bovis from the host and preventing the specific lung lesions, indicating an ability of the pathogen to avoid the host immune response in the M. bovis pneumonia. Full article
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11 pages, 261 KiB  
Article
Barcoding of the Genus Culicoides (Diptera: Ceratopogonidae) in Austria—An Update of the Species Inventory Including the First Records of Three Species in Austria
by Carina Zittra, Günther Wöss, Lara Van der Vloet, Karin Bakran-Lebl, Bita Shahi Barogh, Peter Sehnal and Hans-Peter Fuehrer
Pathogens 2020, 9(5), 406; https://doi.org/10.3390/pathogens9050406 - 23 May 2020
Cited by 10 | Viewed by 3096
Abstract
Ceratopogonidae are small nematoceran Diptera with a worldwide distribution, consisting of more than 5400 described species, divided into 125 genera. The genus Culicoides is known to comprise hematophagous vectors of medical and veterinary importance. Diseases transmitted by Culicoides spp. Such as African horse [...] Read more.
Ceratopogonidae are small nematoceran Diptera with a worldwide distribution, consisting of more than 5400 described species, divided into 125 genera. The genus Culicoides is known to comprise hematophagous vectors of medical and veterinary importance. Diseases transmitted by Culicoides spp. Such as African horse sickness virus, Bluetongue virus, equine encephalitis virus (Reoviridae) and Schmallenberg virus (Bunyaviridae) affect large parts of Europe and are strongly linked to the spread and abundance of its vectors. However, Culicoides surveillance measures are not implemented regularly nor in the whole of Austria. In this study, 142 morphologically identified individuals were chosen for molecular analyses (barcoding) of the mitochondrial cytochrome c oxidase subunit I gene (mt COI). Molecular analyses mostly supported previous morphologic identification. Mismatches between results of molecular and morphologic analysis revealed three new Culicoides species in Austria, Culicoides gornostaevae Mirzaeva, 1984, which is a member of the Obsoletus group, C. griseidorsum Kieffer, 1918 and C. pallidicornis Kieffer, 1919 as well as possible cryptic species. We present here the first Austrian barcodes of the mt COI region of 26 Culicoides species and conclude that barcoding is a reliable tool with which to support morphologic analysis, especially with regard to the difficult to identify females of the medically and economically important genus Culicoides. Full article
17 pages, 1712 KiB  
Review
Drug Discovery against Acanthamoeba Infections: Present Knowledge and Unmet Needs
by Hany M. Elsheikha, Ruqaiyyah Siddiqui and Naveed Ahmed Khan
Pathogens 2020, 9(5), 405; https://doi.org/10.3390/pathogens9050405 - 22 May 2020
Cited by 36 | Viewed by 5486
Abstract
Although major strides have been made in developing and testing various anti-acanthamoebic drugs, recurrent infections, inadequate treatment outcomes, health complications, and side effects associated with the use of currently available drugs necessitate the development of more effective and safe therapeutic regimens. For any [...] Read more.
Although major strides have been made in developing and testing various anti-acanthamoebic drugs, recurrent infections, inadequate treatment outcomes, health complications, and side effects associated with the use of currently available drugs necessitate the development of more effective and safe therapeutic regimens. For any new anti-acanthamoebic drugs to be more effective, they must have either superior potency and safety or at least comparable potency and an improved safety profile compared to the existing drugs. The development of the so-called ‘next-generation’ anti-acanthamoebic agents to address this challenge is an active area of research. Here, we review the current status of anti-acanthamoebic drugs and discuss recent progress in identifying novel pharmacological targets and new approaches, such as drug repurposing, development of small interfering RNA (siRNA)-based therapies and testing natural products and their derivatives. Some of the discussed approaches have the potential to change the therapeutic landscape of Acanthamoeba infections. Full article
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14 pages, 1351 KiB  
Review
A Review: Wolbachia-Based Population Replacement for Mosquito Control Shares Common Points with Genetically Modified Control Approaches
by Pei-Shi Yen and Anna-Bella Failloux
Pathogens 2020, 9(5), 404; https://doi.org/10.3390/pathogens9050404 - 22 May 2020
Cited by 43 | Viewed by 7938
Abstract
The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium [...] Read more.
The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium Wolbachia, endowing a pathogen-blocking phenotype, is considered an environmentally friendly strategy to replace the target population for controlling arboviral diseases. However, the incomplete knowledge regarding the pathogen-blocking mechanism weakens the reliability of a Wolbachia-based population replacement strategy. Wolbachia infections are also vulnerable to environmental factors, temperature, and host diet, affecting their densities in mosquitoes and thus the virus-blocking phenotype. Here, we review the properties of the Wolbachia strategy as an approach to control mosquito populations in comparison with genetically modified control methods. Both strategies tend to limit arbovirus infections but increase the risk of selecting arbovirus escape mutants, rendering these strategies less reliable. Full article
(This article belongs to the Special Issue Untargeted Alternative Routes of Arbovirus Transmission)
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16 pages, 2368 KiB  
Review
The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers
by Claire D. James, Iain M. Morgan and Molly L. Bristol
Pathogens 2020, 9(5), 403; https://doi.org/10.3390/pathogens9050403 - 22 May 2020
Cited by 20 | Viewed by 6184
Abstract
High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen [...] Read more.
High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen signaling and describe both pro and potentially anti-cancer effects of this hormone in HPV-positive cancers. This review will summarize: (1) cell culture-related evidence, (2) animal model evidence, and (3) clinical evidence demonstrating an interaction between estrogen and HPV-positive cancers. This comprehensive review provides insights into the potential relationship between estrogen and HPV. We suggest that estrogen may provide a potential therapeutic for HPV-related cancers, however additional studies are necessary. Full article
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14 pages, 3625 KiB  
Article
A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation
by Kristen A. Johnson, Rudramani Pokhrel, Melissa R. Budicini, Bernard S. Gerstman, Prem P. Chapagain and Robert V. Stahelin
Pathogens 2020, 9(5), 402; https://doi.org/10.3390/pathogens9050402 - 22 May 2020
Cited by 7 | Viewed by 3199
Abstract
The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions [...] Read more.
The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions during the viral life cycle, although the structural dynamics of eVP40 that warrant dimer, hexamer, and octamer formation are still poorly understood. eVP40 has two conserved Trp residues at positions 95 and 191. The role of Trp95 has been characterized in depth as it serves as an important residue in eVP40 oligomer formation. To gain insight into the functional role of Trp191 in eVP40, we prepared mutations of Trp191 (W191A or W191F) to determine the effects of mutation on eVP40 plasma membrane localization and budding as well as eVP40 oligomerization. These in vitro and cellular experiments were complemented by molecular dynamics simulations of the wild-type (WT) eVP40 structure versus that of W191A. Taken together, Trp is shown to be a critical amino acid at position 191 as mutation to Ala reduces the ability of VP40 to localize to the plasma membrane inner leaflet and form new virus-like particles. Further, mutation of Trp191 to Ala or Phe shifted the in vitro equilibrium to the octamer form by destabilizing Trp191 interactions with nearby residues. This study has shed new light on the importance of interdomain interactions in stability of the eVP40 structure and the critical nature of timing of eVP40 oligomerization for plasma membrane localization and viral budding. Full article
(This article belongs to the Section Viral Pathogens)
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7 pages, 1263 KiB  
Article
Simultaneous Nasal Carriage by Methicillin-Resistant and Methicillin Susceptible Staphylococcus aureus of Lineage ST398 in a Live Pig Transporter
by Paula Gómez, Carmen Aspiroz, Nazreen F. Hadjirin, Daniel Benito, Myriam Zarazaga, Carmen Torres and Mark A. Holmes
Pathogens 2020, 9(5), 401; https://doi.org/10.3390/pathogens9050401 - 21 May 2020
Cited by 3 | Viewed by 2221
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST)398 is a livestock associated (LA) lineage with zoonotic potential, especially in humans with live pig contact. The objective of this study was to characterize two S. aureus strains of lineage ST398 (one methicillin-resistant (MRSA), one methicillin-susceptible [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST)398 is a livestock associated (LA) lineage with zoonotic potential, especially in humans with live pig contact. The objective of this study was to characterize two S. aureus strains of lineage ST398 (one methicillin-resistant (MRSA), one methicillin-susceptible (MSSA)) isolated from the same nasal sample of a patient admitted in the Intensive-Care Unit of a Spanish Hospital, and with previous occupational exposure to live pigs, by whole-genome-sequencing (WGS). The sample was obtained during routine surveillance for MRSA colonization. Purified genomic DNA was sequenced using Illumina HiSeq 2000 and processed using conventional bioinformatics software. The two isolates recovered were both S. aureus t011/ST398 and showed similar resistance-phenotypes, other than methicillin susceptibility. The possession of antibiotic resistance genes was the same, except for the mecA-gene located in SCCmecV in the MRSA isolate. The MSSA isolate harbored remnants of a SCCmec following the deletion of 17342bp from a recombination between two putative primases. Both isolates belonged to the livestock-associated clade as defined by three canonical single-nucleotide-polymorphisms, and neither possessed the human immune evasion cluster genes, chp, scn, or sak. The core genome alignment showed a similarity of 99.6%, and both isolates harbored the same mobile genetic elements. The two nasal ST398 isolates recovered from the patient with previous occupational exposure to pigs appeared to have a livestock origin and could represent different evolutionary steps of animal-human interface lineage. The MSSA strain was formed as a result of the loss of the mecA gene from the livestock-associated-MRSA lineage. Full article
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23 pages, 1193 KiB  
Review
Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond
by Pragyesh Dhungel, Fernando M. Cantu, Joshua A. Molina and Zhilong Yang
Pathogens 2020, 9(5), 400; https://doi.org/10.3390/pathogens9050400 - 21 May 2020
Cited by 14 | Viewed by 7375
Abstract
The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host [...] Read more.
The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host shutoff”. To induce host shutoff, a virus may target various steps of gene expression, as well as pre- and post-gene expression processes. During infection, vaccinia virus (VACV), the prototype poxvirus, targets all major processes of the central dogma of genetics, as well as pre-transcription and post-translation steps to hinder host cell protein production. In this article, we review the strategies used by VACV to induce host shutoff in the context of strategies employed by other viruses. We elaborate on how VACV induces host shutoff by targeting host cell DNA synthesis, RNA production and processing, mRNA translation, and protein degradation. We emphasize the topics on VACV’s approaches toward modulating mRNA processing, stability, and translation during infection. Finally, we propose avenues for future investigations, which will facilitate our understanding of poxvirus biology, as well as fundamental cellular gene expression and regulation mechanisms. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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21 pages, 1734 KiB  
Article
LC-QTOF-MS and 1H NMR Metabolomics Verifies Potential Use of Greater Omentum for Klebsiella pneumoniae Biofilm Eradication in Rats
by Joanna Teul, Stanisław Deja, Katarzyna Celińska-Janowicz, Adam Ząbek, Piotr Młynarz, Piotr Barć, Adam Junka, Danuta Smutnicka, Marzenna Bartoszewicz, Jerzy Pałka and Wojciech Miltyk
Pathogens 2020, 9(5), 399; https://doi.org/10.3390/pathogens9050399 - 21 May 2020
Cited by 3 | Viewed by 2446
Abstract
Bacterial wound infections are a common problem associated with surgical interventions. In particular, biofilm-forming bacteria are hard to eradicate, and alternative methods of treatment based on covering wounds with vascularized flaps of tissue are being developed. The greater omentum is a complex organ [...] Read more.
Bacterial wound infections are a common problem associated with surgical interventions. In particular, biofilm-forming bacteria are hard to eradicate, and alternative methods of treatment based on covering wounds with vascularized flaps of tissue are being developed. The greater omentum is a complex organ covering the intestines in the abdomen, which support wound recovery following surgical procedures and exhibit natural antimicrobial activity that could improve biofilm eradication. We investigated changes in rats’ metabolome following Klebsiella pneumoniae infections, as well as the greater omentum’s ability for Klebsiella pneumoniae biofilm eradication. Rats received either sterile implants or implants covered with Klebsiella pneumoniae biofilm (placed in the peritoneum or greater omentum). Metabolic profiles were monitored at days 0, 2, and 5 after surgery using combined proton nuclear magnetic resonance (1H NMR) and high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC–QTOF-MS) measurements of urine samples followed by chemometric analysis. Obtained results indicated that grafting of the sterile implant to the greater omentum did not cause major disturbances in rats’ metabolism, whereas the sterile implant located in the peritoneum triggered metabolic perturbations related to tricarboxylic acid (TCA) cycle, as well as choline, tryptophan, and hippurate metabolism. Presence of implants colonized with Klebsiella pneumoniae biofilm resulted in similar levels of metabolic perturbations in both locations. Our findings confirmed that surgical procedures utilizing the greater omentum may have a practical use in wound healing and tissue regeneration in the future. Full article
(This article belongs to the Section Human Pathogens)
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14 pages, 1473 KiB  
Article
Opportunistic Mapping of Strongyloides stercoralis and Hookworm in Dogs in Remote Australian Communities
by Meruyert Beknazarova, Harriet Whiley, Rebecca Traub and Kirstin Ross
Pathogens 2020, 9(5), 398; https://doi.org/10.3390/pathogens9050398 - 21 May 2020
Cited by 14 | Viewed by 3341
Abstract
Both Strongyloides stercoralis and hookworms are common soil-transmitted helminths in remote Australian communities. In addition to infecting humans, S. stercoralis and some species of hookworms infect canids and therefore present both environmental and zoonotic sources of transmission to humans. Currently, there is limited [...] Read more.
Both Strongyloides stercoralis and hookworms are common soil-transmitted helminths in remote Australian communities. In addition to infecting humans, S. stercoralis and some species of hookworms infect canids and therefore present both environmental and zoonotic sources of transmission to humans. Currently, there is limited information available on the prevalence of hookworms and S. stercoralis infections in dogs living in communities across the Northern Territory in Australia. In this study, 274 dog faecal samples and 11 faecal samples of unknown origin were collected from the environment and directly from animals across 27 remote communities in Northern and Central Australia. Samples were examined using real-time polymerase chain reaction (PCR) analysis for the presence of S. stercoralis and four hookworm species: Ancylostoma caninum, Ancylostoma ceylanicum, Ancylostoma braziliense and Uncinaria stenocephala. The prevalence of S. stercoralis in dogs was found to be 21.9% (60/274). A. caninum was the only hookworm detected in the dog samples, with a prevalence of 31.4% (86/274). This study provides an insight into the prevalence of S. stercoralis and hookworms in dogs and informs future intervention and prevention strategies aimed at controlling these parasites in both dogs and humans. A “One Health” approach is crucial for the prevention of these diseases in Australia. Full article
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15 pages, 8034 KiB  
Article
First Isolation and Characterization of Chryseobacterium cucumeris SKNUCL01, Isolated from Diseased Pond loach (Misgurnus anguillicaudatus) in Korea
by Sang Guen Kim, Sib Sankar Giri, Sang Wha Kim, Jun Kwon, Sung Bin Lee and Se Chang Park
Pathogens 2020, 9(5), 397; https://doi.org/10.3390/pathogens9050397 - 21 May 2020
Cited by 6 | Viewed by 3194
Abstract
Loaches are widely distributed throughout the natural environment and are consumed for medicinal purposes in East Asia. Usually, loaches are cultured in ponds where the water conditions can easily cause bacterial infections. Infections due to bacterial pathogens such as Aeromonas have been well [...] Read more.
Loaches are widely distributed throughout the natural environment and are consumed for medicinal purposes in East Asia. Usually, loaches are cultured in ponds where the water conditions can easily cause bacterial infections. Infections due to bacterial pathogens such as Aeromonas have been well described in cultured loaches; however, there is no report regarding Chryseobacterium infection. This study focused on the elucidation of the pathogenic and antibiotic resistance characteristics of C. cucumeris, SKNUCL01, isolated from diseased loaches (Misgurnus anguillicaudatus). SKNUCL01 forms a biofilm, which is associated with its virulence. Koch’s postulates were satisfied with a lethal dose 50 (LD50) of 8.52 × 107 colony-forming units (CFU)/ml. Abrasion facilitates the mortality of the fish, which makes it a possible infection route for C. cucumeris. The strain showed resistance to nearly all tested antibiotics, such as trimethoprim/sulfamethoxazole, levofloxacin, and ciprofloxacin, formerly considered effective treatments. Phenotypic analyses for antibiotic resistance—the combined disk test, double-disk synergy test, modified Hodge test, and efflux pump inhibition test—revealed that the resistance of SKNUCL01 originated from metallo-beta lactamases (MBLs) and efflux pumps. Our findings provide evidence that could result in a breakthrough against multidrug-resistant Chryseobacterium infection in the aquaculture industry; the antibiotic resistance-related genes can be elucidated through future study. Full article
(This article belongs to the Special Issue Emerging Infectious Diseases in Aquaculture)
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9 pages, 530 KiB  
Article
Characteristics of Serotype 3 Invasive Pneumococcal Disease before and after Universal Childhood Immunization with PCV13 in Massachusetts
by Rotem Lapidot, Kimberly M. Shea, Inci Yildirim, Howard J. Cabral, Stephen I. Pelton and the Massachusetts Department of Public Health
Pathogens 2020, 9(5), 396; https://doi.org/10.3390/pathogens9050396 - 21 May 2020
Cited by 22 | Viewed by 2949
Abstract
Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the [...] Read more.
Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the impact of PCV13 on serotype 3 IPD incidence and disease characteristics in Massachusetts’ children. Methods: Serotype 3 IPD cases in children <18 years old were identified via enhanced passive surveillance system in Massachusetts. We compared incidence rates and characteristics of IPD cases before and after PCV13. Results: A total of 47 serotype 3 IPD cases were identified from 2002 to 2017; incidence of serotype 3 IPD in the years following PCV13 was 0.19 per 100,000 children compared to 0.21 before PCV 13, incidence rate ratio (IRR) = 0.86 (95% CI 0.47–1.57). The majority (78%) of post-PCV13 serotype 3 IPD cases occurred among fully vaccinated children. Age distribution, clinical syndrome and presence of comorbidities among serotype 3 IPD cases were similar before and after PCV13 introduction. There was no association between the date of the last PCV13 dose and time to IPD to suggest waning of immunity. Conclusions: seven years following PCV 13 we found no significant changes in serotype 3 IPD incidence or disease characteristics in children in Massachusetts. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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14 pages, 3830 KiB  
Article
Microbiological and Histological Analysis for the Evaluation of Farmed Mussels (Mytilus galloprovincialis) Health Status, in Coastal Areas of Italy
by Roberta Battistini, Katia Varello, Valeria Listorti, Michela Zambon, Giuseppe Arcangeli, Elena Bozzetta, Danila Raffaella Francese, Carlo Ercolini and Laura Serracca
Pathogens 2020, 9(5), 395; https://doi.org/10.3390/pathogens9050395 - 21 May 2020
Cited by 1 | Viewed by 3034
Abstract
Shellfish farming is a relevant economic activity in Italy. The Gulf of La Spezia is one of the major production areas for mussels: the area is characterized by the presence of numerous human activities that could harm the quality of seawater. Additionally, the [...] Read more.
Shellfish farming is a relevant economic activity in Italy. The Gulf of La Spezia is one of the major production areas for mussels: the area is characterized by the presence of numerous human activities that could harm the quality of seawater. Additionally, the presence of potentially pathogenic microorganisms may influence the health status of animals, which must be constantly monitored. To have a clear view of the health conditions of the mussels (Mytilus galloprovincialis) farmed in this area, microbiological, parasitological, and histological analyses were performed. The study was conducted from November 2016 to October 2017. Overall, despite the presence of potentially pathogenic microorganisms for mussels, abnormal mortality rates were not reported during the monitoring period and the histological examination revealed no significant lesions. Our study confirms that studying different aspects together is a useful tool for assessing the health conditions of mussels and points out the importance of adverse environmental conditions for the expression of the pathogenicity of microorganisms. Full article
(This article belongs to the Special Issue Spontaneous Diseases of Mollusks)
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12 pages, 2058 KiB  
Article
Seroprevalence of the Strongyloides stercoralis Infection in Humans from Yungas Rainforest and Gran Chaco Region from Argentina and Bolivia
by Rubén O. Cimino, Pedro Fleitas, Mariana Fernández, Adriana Echazú, Marisa Juarez, Noelia Floridia-Yapur, Pamela Cajal, Alfredo Seijo, Marcelo Abril, Diego Weinberg, Pablo Piorno, Nicolás Caro, Paola Vargas, José Gil, Favio Crudo and Alejandro Krolewiecki
Pathogens 2020, 9(5), 394; https://doi.org/10.3390/pathogens9050394 - 20 May 2020
Cited by 6 | Viewed by 3009
Abstract
The threadworm, Strongyloides stercoralis, is endemic in tropical and subtropical areas. Data on the prevalence and distribution of infection with this parasite species is scarce in many critical regions. We conducted a seroprevalence study of S. stercoralis infection in 13 locations in [...] Read more.
The threadworm, Strongyloides stercoralis, is endemic in tropical and subtropical areas. Data on the prevalence and distribution of infection with this parasite species is scarce in many critical regions. We conducted a seroprevalence study of S. stercoralis infection in 13 locations in the Gran Chaco and Yungas regions of Argentina and Bolivia during the period 2010–2016. A total of 2803 human serum samples were analyzed by ELISA-NIE which has a sensitivity of 75% and specificity of 95%. Results showed that 551 (19.6%) of those samples were positive. The adjusted prevalence was 20.9%, (95% confidence interval (CI) 19.4–22.4%). The distribution of cases was similar between females and males with an increase of prevalence with age. The prevalence in the different locations ranged from 7.75% in Pampa del Indio to 44.55% in Santa Victoria Este in the triple border between Argentina, Bolivia, and Paraguay in the Chaco region. Our results show that S. stercoralis is highly prevalent in the Chaco and Yungas regions, which should prompt prospective surveys to confirm our findings and the design and deployment of control measures. Full article
(This article belongs to the Special Issue Prevalence of Strongyloidiasis and Schistosomiasis)
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16 pages, 4200 KiB  
Article
Infectivity and Drug Susceptibility Profiling of Different Leishmania-Host Cell Combinations
by Kyung-Hwa Baek, Laura Piel, Thibault Rosazza, Eric Prina, Gerald F. Späth and Joo Hwan No
Pathogens 2020, 9(5), 393; https://doi.org/10.3390/pathogens9050393 - 20 May 2020
Cited by 13 | Viewed by 3594
Abstract
Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a spectrum of a disease that threatens public health worldwide. Although next-generation therapeutics are urgently needed, the early stage of the drug discovery process is hampered by very low hit rates [...] Read more.
Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a spectrum of a disease that threatens public health worldwide. Although next-generation therapeutics are urgently needed, the early stage of the drug discovery process is hampered by very low hit rates from intracellular Leishmania phenotypic high-throughput screenings. Designing and applying a physiologically relevant in vitro assay is therefore in high demand. In this study, we characterized the infectivity, morphology, and drug susceptibility of different Leishmania and host cell infection combinations. Primary bone marrow-derived macrophage (BMDM) and differentiated human acute monocytic leukemia (THP-1) cells were infected with amastigote or promastigote forms of Leishmania amazonensis and Leishmania donovani. Regardless of host cell types, amastigotes were generally well phagocytosed and showed high infectivity, whereas promastigotes, especially those of L. donovani, had predominantly remained in the extracellular space. In the drug susceptibility test, miltefosine and sodium stibogluconate (SSG) showed varying ranges of activity with 14 and >10-fold differences in susceptibility, depending on the host-parasite pairs, indicating the importance of assay conditions for evaluating antileishmanial activity. Overall, our results suggest that combinations of Leishmania species, infection forms, and host cells must be carefully optimized to evaluate the activity of potential therapeutic compounds against Leishmania. Full article
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14 pages, 624 KiB  
Article
Hepatitis E Virus Seroprevalence and Associated Risk Factors in Apparently Healthy Individuals from Osun State, Nigeria
by Folakemi Abiodun Osundare, Patrycja Klink, Catharina Majer, Olusola Aanuoluwapo Akanbi, Bo Wang, Mirko Faber, Dominik Harms, C.-Thomas Bock and Oladele Oluyinka Opaleye
Pathogens 2020, 9(5), 392; https://doi.org/10.3390/pathogens9050392 - 20 May 2020
Cited by 5 | Viewed by 3023
Abstract
Hepatitis E virus (HEV) infection is a major public health concern in low-income countries, yet incidence and prevalence estimates are often lacking. Serum (n = 653) and faecal (n = 150) samples were collected from apparently healthy individuals using convenience sampling [...] Read more.
Hepatitis E virus (HEV) infection is a major public health concern in low-income countries, yet incidence and prevalence estimates are often lacking. Serum (n = 653) and faecal (n = 150) samples were collected from apparently healthy individuals using convenience sampling technique in six communities (Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo) from Osun State, Nigeria. Serum samples were analysed for total anti-HEV IgG/IgM and anti-HEV IgM using commercially available HEV ELISA kits. Total anti-HEV positive serum and all stool samples were analysed for HEV RNA by RT-PCR. Overall, 15.0% (n = 98/653) and 3.8% (n = 25/653) of the serum samples were positive for anti-HEV total and IgM antibodies, respectively. Total anti-HEV and IgM in Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo was 21.0% (n = 13/62) and 3.2% (n = 2/62), 19.4% (n = 20/103) and 6.8% (n = 7/103), 11.4% (n = 12/105) and 2.9% (n = 3/105), 8.0% (n = 16/199) and 1.5% (n = 3/199), 22.0% (n = 22/100) and 10.0% (n = 10/100), and 17.9% (n = 15/84) and 0.0% (n = 0/84), respectively. All samples (stool and serum) were HEV RNA negative. Anti-HEV seroprevalence was associated with rural location, increasing age, alcohol consumption, and rearing of animals. This study demonstrated a high anti-HEV seroprevalence in Osun State, indicating the need to implement surveillance and asses the hepatitis E burden in Nigeria. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)
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17 pages, 1519 KiB  
Article
Uncovering the First Atypical DS-1-like G1P[8] Rotavirus Strains That Circulated during Pre-Rotavirus Vaccine Introduction Era in South Africa
by Peter N. Mwangi, Milton T. Mogotsi, Sebotsana P. Rasebotsa, Mapaseka L. Seheri, M. Jeffrey Mphahlele, Valantine N. Ndze, Francis E. Dennis, Khuzwayo C. Jere and Martin M. Nyaga
Pathogens 2020, 9(5), 391; https://doi.org/10.3390/pathogens9050391 - 20 May 2020
Cited by 17 | Viewed by 3226
Abstract
Emergence of DS-1-like G1P[8] group A rotavirus (RVA) strains during post-rotavirus vaccination period has recently been reported in several countries. This study demonstrates, for the first time, rare atypical DS-1-like G1P[8] RVA strains that circulated in 2008 during pre-vaccine era in South Africa. [...] Read more.
Emergence of DS-1-like G1P[8] group A rotavirus (RVA) strains during post-rotavirus vaccination period has recently been reported in several countries. This study demonstrates, for the first time, rare atypical DS-1-like G1P[8] RVA strains that circulated in 2008 during pre-vaccine era in South Africa. Rotavirus positive samples were subjected to whole-genome sequencing. Two G1P[8] strains (RVA/Human-wt/ZAF/UFS-NGS-MRC-DPRU1971/2008/G1P[8] and RVA/Human-wt/ZAF/UFS-NGS-MRC-DPRU1973/2008/G1P[8]) possessed a DS-1-like genome constellation background (I2-R2-C2-M2-A2-N2-T2-E2-H2). The outer VP4 and VP7 capsid genes of the two South African G1P[8] strains had the highest nucleotide (amino acid) nt (aa) identities of 99.6–99.9% (99.1–100%) with the VP4 and the VP7 genes of a locally circulating South African strain, RVA/Human-wt/ZAF/MRC-DPRU1039/2008/G1P[8]. All the internal backbone genes (VP1–VP3, VP6, and NSP1-NSP5) had the highest nt (aa) identities with cognate internal genes of another locally circulating South African strain, RVA/Human-wt/ZAF/MRC-DPRU2344/2008/G2P[6]. The two study strains emerged through reassortment mechanism involving locally circulating South African strains, as they were distinctly unrelated to other reported atypical G1P[8] strains. The identification of these G1P[8] double-gene reassortants during the pre-vaccination period strongly supports natural RVA evolutionary mechanisms of the RVA genome. There is a need to maintain long-term whole-genome surveillance to monitor such atypical strains. Full article
(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)
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11 pages, 288 KiB  
Article
Multiple Tick-Borne Pathogens in Ixodes ricinus Ticks Collected from Humans in Romania
by Zsuzsa Kalmár, Mirabela Oana Dumitrache, Gianluca D’Amico, Ioana Adriana Matei, Angela Monica Ionică, Călin Mircea Gherman, Mihaela Lupșe and Andrei Daniel Mihalca
Pathogens 2020, 9(5), 390; https://doi.org/10.3390/pathogens9050390 - 19 May 2020
Cited by 12 | Viewed by 3201
Abstract
Ticks are medically important vectors of infectious diseases that are able to transmit pathogens to humans and animals. Tick-borne diseases represent a major health concern, posing an increasing risk to the public health during the last century and affecting millions of people. The [...] Read more.
Ticks are medically important vectors of infectious diseases that are able to transmit pathogens to humans and animals. Tick-borne diseases represent a major health concern, posing an increasing risk to the public health during the last century and affecting millions of people. The aim of the current study was to provide epidemiological data regarding the presence of certain tick-borne pathogens in ticks feeding on humans in Romania. Overall, 522 Ixodes ricinus ticks collected from humans were screened for six pathogens: Borrelia spp., Neoehrlichia mikurensis, Babesia spp., Coxiella spp., Bartonella spp., and Francisella tularensis. Ticks attached to humans were collected between 2013–2015 in Cluj County, Romania. Conventional, nested and quantitative PCR were used to detect specific genetic sequences of each pathogen. For identifying the infectious agents, positive samples were sequenced. The infection prevalence was 21.07% from which 8.18% were mixed infections. The detected agents were Borrelia spp., N. mikurensis and Babesia spp. The present data reveal the endemic occurrence of potentially zoonotic pathogens in Romania. Revealing the current distribution of tick-borne pathogens in ticks collected from humans may provide new insights in understanding the complex ecology of tick-borne diseases and enlightens current knowledge about the infection prevalence at local, regional and national levels. Full article
13 pages, 764 KiB  
Review
The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?
by Shelley A. Cole, Hugo A. Laviada-Molina, Jeannette M. Serres-Perales, Ernesto Rodriguez-Ayala and Raul A. Bastarrachea
Pathogens 2020, 9(5), 389; https://doi.org/10.3390/pathogens9050389 - 19 May 2020
Cited by 13 | Viewed by 7760
Abstract
An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the [...] Read more.
An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection. Full article
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8 pages, 536 KiB  
Article
Should We Screen HIV-Positive Migrants for Strongyloidiasis?
by Caroline Theunissen, Emmanuel Bottieau, Marjan Van Esbroeck, Achilleas Tsoumanis and Eric Florence
Pathogens 2020, 9(5), 388; https://doi.org/10.3390/pathogens9050388 - 18 May 2020
Cited by 3 | Viewed by 2552
Abstract
Background: Strongyloides stercoralis, a nematode endemic in all (sub)tropical regions, can cause life-threatening disease, especially in immunosuppressed patients. Many countries with high HIV-prevalence rates are also highly S. stercoralis endemic, and co-infection may occur. Methods: Retrospective study based on serological testing for S. [...] Read more.
Background: Strongyloides stercoralis, a nematode endemic in all (sub)tropical regions, can cause life-threatening disease, especially in immunosuppressed patients. Many countries with high HIV-prevalence rates are also highly S. stercoralis endemic, and co-infection may occur. Methods: Retrospective study based on serological testing for S. stercoralis in all HIV-infected migrants followed at the Institute of Tropical Medicine, Antwerp, Belgium. If untested, serologic testing was performed on stored samples, dating from the first HIV viral load determination. The epidemiological, clinical and laboratory features of patients with and without strongyloidiasis were retrieved from the electronic medical files. Results: Of the 2846 HIV patients in active follow-up, 723 (25.4%) had a migration background. Thirty-six patients (5.1%) were diagnosed with Strongyloides co-infection, including 29 during their medical evaluation and seven retrospectively. Patients had a median age of 35.3 years (IQR 30.3–44.4), 28 patients (78%) originated from Sub-Saharan Africa and median time in Belgium was 3.5 years (IQR 0.8–5.7). Symptoms compatible with strongyloidiasis were present in 17 (47%) patients, of whom two were diagnosed retrospectively. Eosinophilia (eosinophil cell count > 450/µL) was observed in 19 (53%) participants. Median CD4 level was 386 /µL (IQR 299–518) at diagnosis of co-infection. Of note, 8 (22%) patients with strongyloidiasis had no reported symptoms nor eosinophilia. None of the patients developed hyperinfection syndrome. There were no differences in age, gender, geographic origin, clinical presentation, CD4 level or viral load between patients with and without strongyloidiasis. Only eosinophilia was strongly correlated with the presence of Strongyloides in multivariate analysis (OR 10.74 (95% CI 5.19–22.25), p < 0.001); the positive likelihood ratio (LR+) of eosinophilia for strongyloidiasis was 5.38 (95% CI 3.66–7.91). Conclusion: Strongyloidiasis was diagnosed in 5.1% of HIV-infected migrants. Eosinophilia had good confirming power for the presence of the disease. However, a sizeable proportion (22%) of co-infected individuals were asymptomatic and had normal eosinophil count, supporting universal screening of all HIV-positive patients native to tropical countries. Full article
(This article belongs to the Special Issue Prevalence of Strongyloidiasis and Schistosomiasis)
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15 pages, 2841 KiB  
Article
Streptococcus suis Uptakes Carbohydrate Source from Host Glycoproteins by N-glycans Degradation System for Optimal Survival and Full Virulence during Infection
by Jiale Ma, Ze Zhang, Zihao Pan, Qiankun Bai, Xiaojun Zhong, Yinchu Zhu, Yue Zhang, Zongfu Wu, Guangjin Liu and Huochun Yao
Pathogens 2020, 9(5), 387; https://doi.org/10.3390/pathogens9050387 - 18 May 2020
Cited by 4 | Viewed by 2828
Abstract
Infection with the epidemic virulent strain of Streptococcus suis serotype 2 (SS2) can cause septicemia in swine and humans, leading to pneumonia, meningitis and even cytokine storm of Streptococcal toxic shock-like syndrome. Despite some progress concerning the contribution of bacterial adhesion, biofilm, toxicity [...] Read more.
Infection with the epidemic virulent strain of Streptococcus suis serotype 2 (SS2) can cause septicemia in swine and humans, leading to pneumonia, meningitis and even cytokine storm of Streptococcal toxic shock-like syndrome. Despite some progress concerning the contribution of bacterial adhesion, biofilm, toxicity and stress response to the SS2 systemic infection, the precise mechanism underlying bacterial survival and growth within the host bloodstream remains elusive. Here, we reported the SS2 virulent strains with a more than 20 kb endoSS-related insertion region that showed significantly higher proliferative ability in swine serum than low-virulent strains. Further study identified a complete N-glycans degradation system encoded within this insertion region, and found that both GH92 and EndoSS contribute to bacterial virulence, but that only DndoSS was required for optimal growth of SS2 in host serum. The supplement of hydrolyzed high-mannose-containing glycoprotein by GH92 and EndoSS could completely restore the growth deficiency of endoSS deletion mutant in swine serum. EndoSS only hydrolyzed a part of the model glycoprotein RNase B with high-mannose N-linked glycoforms into a low molecular weight form, and the solo activity of GH92 could not show any changes comparing with the blank control in SDS-PAGE gel. However, complete hydrolyzation was observed under the co-incubation of EndoSS and GH92, suggesting GH92 may degrade the high-mannose arms of N-glycans to generate a substrate for EndoSS. In summary, these findings provide compelling evidences that EndoSS-related N-glycans degradation system may enable SS2 to adapt to host serum-specific availability of carbon sources from glycoforms, and be required for optimal colonization and full virulence during systemic infection. Full article
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18 pages, 1820 KiB  
Article
Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota
by Sigri Kløve, Claudia Genger, Soraya Mousavi, Dennis Weschka, Stefan Bereswill and Markus M. Heimesaat
Pathogens 2020, 9(5), 386; https://doi.org/10.3390/pathogens9050386 - 18 May 2020
Cited by 12 | Viewed by 2936
Abstract
Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate [...] Read more.
Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10-/- mice and IL10-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10-/- counterparts. Furthermore, C. coli infected IL10-/-, as opposed to TLR4-deficient IL10-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail. Full article
(This article belongs to the Special Issue Campylobacter Infections)
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4 pages, 194 KiB  
Editorial
Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment
by Riccardo Miggiano, Menico Rizzi and Davide M. Ferraris
Pathogens 2020, 9(5), 385; https://doi.org/10.3390/pathogens9050385 - 18 May 2020
Cited by 29 | Viewed by 10159
Abstract
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB) and it represents a persistent public health threat for a number of complex biological and sociological reasons. According to the most recent Global Tuberculosis Report (2019) edited by the World [...] Read more.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB) and it represents a persistent public health threat for a number of complex biological and sociological reasons. According to the most recent Global Tuberculosis Report (2019) edited by the World Health Organization (WHO), TB is considered the ninth cause of death worldwide and the leading cause of mortality by a single infectious agent, with the highest rate of infections and death toll rate mostly concentrated in developing and low-income countries. We present here the editorial section to the Special Issue entitled “Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment” that includes 7 research articles and a review. The scientific contributions included in the Special Issue mainly focus on the characterization of MTB strains emerging in TB endemic countries as well as on multiple mechanisms adopted by the bacteria to resist and to adapt to antitubercular therapies. Full article
44 pages, 1036 KiB  
Review
From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts
by Ragab M. Fereig and Yoshifumi Nishikawa
Pathogens 2020, 9(5), 384; https://doi.org/10.3390/pathogens9050384 - 16 May 2020
Cited by 25 | Viewed by 3927
Abstract
Neospora caninum is an intracellular protozoan parasite affecting numerous animal species. It induces significant economic losses because of abortion and neonatal abnormalities in cattle. In case of infection, the parasite secretes numerous arsenals to establish a successful infection in the host cell. In [...] Read more.
Neospora caninum is an intracellular protozoan parasite affecting numerous animal species. It induces significant economic losses because of abortion and neonatal abnormalities in cattle. In case of infection, the parasite secretes numerous arsenals to establish a successful infection in the host cell. In the same context but for a different purpose, the host resorts to different strategies to eliminate the invading parasite. During this battle, numerous key factors from both parasite and host sides are produced and interact for the maintaining and vanishing of the infection, respectively. Although several reviews have highlighted the role of different compartments of the immune system against N. caninum infection, each one of them has mostly targeted specific points related to the immune component and animal host. Thus, in the current review, we will focus on effector molecules derived from the host cell or the parasite using a comprehensive survey method from previous reports. According to our knowledge, this is the first review that highlights and discusses immune response at the host cell–parasite molecular interface against N. caninum infection in different susceptible hosts. Full article
(This article belongs to the Special Issue Neospora Caninum: Infection and Immunity)
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11 pages, 1349 KiB  
Article
Influence of the FIV Status and Chronic Gingivitis on Feline Oral Microbiota
by Caitlin E. Older, Márcia de Oliveira Sampaio Gomes, Aline Rodrigues Hoffmann, Mariel Dalmédico Policano, Camila Aparecida Cruz dos Reis, Adriano Bonfim Carregaro, Carlos Eduardo Ambrósio and Valéria Maria Lara Carregaro
Pathogens 2020, 9(5), 383; https://doi.org/10.3390/pathogens9050383 - 16 May 2020
Cited by 13 | Viewed by 3532
Abstract
Feline chronic gingivostomatitis (FCGS) has an unclear pathogenesis with the oral microbiome and viral infections, such as feline immunodeficiency virus (FIV), thought to contribute. Although the relationship between the FIV status and FCGS is not clear, one theory is FIV-induced immune dysregulation could [...] Read more.
Feline chronic gingivostomatitis (FCGS) has an unclear pathogenesis with the oral microbiome and viral infections, such as feline immunodeficiency virus (FIV), thought to contribute. Although the relationship between the FIV status and FCGS is not clear, one theory is FIV-induced immune dysregulation could contribute to oral dysbiosis, promoting FCGS development. To further understand the relationship between FCGS, FIV infection, and the oral microbiome, oral cavities of forty cats fitting within 4 groups (FIV- without gingivitis, FIV+ without gingivitis, FIV- with gingivitis, FIV+ with gingivitis) were swabbed. Next generation sequencing targeting the V4 region of the 16s rRNA gene was performed for bacterial community profiling. No differences in diversity were observed, however, analysis of the data in terms of gingivitis revealed differences in the relative abundance of taxa and predicted functional output. Odoribacter spp., a bacteria associated with oral disease, was found in higher relative abundances in cats with the highest gingivitis grade. Cats with gingivitis were also found to harbor communities more involved in production of short-chain fatty acids, which have been connected with oral disease. Significant findings associated with the FIV status were few and of low impact, suggesting any connection between the FIV status and FCGS is likely not related to the oral microbiota. Full article
(This article belongs to the Section Animal Pathogens)
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