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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Review

9 pages, 629 KiB  
Review
Buffalopox Virus: An Emerging Virus in Livestock and Humans
by Kamal H. Eltom, Abdallah M. Samy, Ahmed Abd El Wahed and Claus-Peter Czerny
Pathogens 2020, 9(9), 676; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9090676 - 20 Aug 2020
Cited by 17 | Viewed by 5459
Abstract
Buffalopox virus (BPXV) is the cause of buffalopox, which was recognized by the FAO/WHO Joint Expert Committee on Zoonosis as an important zoonotic disease. Buffalopox was first described in India, later in other countries, and has become an emerging contagious viral zoonotic disease [...] Read more.
Buffalopox virus (BPXV) is the cause of buffalopox, which was recognized by the FAO/WHO Joint Expert Committee on Zoonosis as an important zoonotic disease. Buffalopox was first described in India, later in other countries, and has become an emerging contagious viral zoonotic disease infecting milkers with high morbidity among affected domestic buffalo and cattle. BPXV is a member of the genus Orthopoxvirus and a close variant of the vaccinia virus (VACV). Recent genome data show that BPXV shares a most recent common ancestor of VACV Lister strain, which had been used for inoculating buffalo calves to produce a Smallpox vaccine. Over time, VACV evolved into BPXV by establishing itself in buffaloes to be increasingly pathogenic to this host and to make infections in cattle and humans. Together with the current pandemic of SARS-COV2/COVID 19, BPXV infections illustrate how vulnerable the human population is to the emergence and re-emergence of viral pathogens from unsuspected sources. In view that majority of the world population are not vaccinated against smallpox and are most vulnerable in the event of its re-emergence, reviewing and understanding the biology of vaccinia-like viruses are necessary for developing a new generation of safer smallpox vaccines in the smallpox-free world. Full article
(This article belongs to the Section Animal Pathogens)
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21 pages, 409 KiB  
Review
Water as a Source of Antimicrobial Resistance and Healthcare-Associated Infections
by Claire Hayward, Kirstin E. Ross, Melissa H. Brown and Harriet Whiley
Pathogens 2020, 9(8), 667; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080667 - 18 Aug 2020
Cited by 21 | Viewed by 5134
Abstract
Healthcare-associated infections (HAIs) are one of the most common patient complications, affecting 7% of patients in developed countries each year. The rise of antimicrobial resistant (AMR) bacteria has been identified as one of the biggest global health challenges, resulting in an estimated 23,000 [...] Read more.
Healthcare-associated infections (HAIs) are one of the most common patient complications, affecting 7% of patients in developed countries each year. The rise of antimicrobial resistant (AMR) bacteria has been identified as one of the biggest global health challenges, resulting in an estimated 23,000 deaths in the US annually. Environmental reservoirs for AMR bacteria such as bed rails, light switches and doorknobs have been identified in the past and addressed with infection prevention guidelines. However, water and water-related devices are often overlooked as potential sources of HAI outbreaks. This systematic review examines the role of water and water-related devices in the transmission of AMR bacteria responsible for HAIs, discussing common waterborne devices, pathogens, and surveillance strategies. AMR strains of previously described waterborne pathogens including Pseudomonas aeruginosa, Mycobacterium spp., and Legionella spp. were commonly isolated. However, methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacteriaceae that are not typically associated with water were also isolated. Biofilms were identified as a hot spot for the dissemination of genes responsible for survival functions. A limitation identified was a lack of consistency between environmental screening scope, isolation methodology, and antimicrobial resistance characterization. Broad universal environmental surveillance guidelines must be developed and adopted to monitor AMR pathogens, allowing prediction of future threats before waterborne infection outbreaks occur. Full article
(This article belongs to the Section Waterborne/Foodborne/Airborne Pathogens)
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17 pages, 653 KiB  
Review
Recent Advances in the Diagnosis of Classical Swine Fever and Future Perspectives
by Lihua Wang, Rachel Madera, Yuzhen Li, David Scott McVey, Barbara S. Drolet and Jishu Shi
Pathogens 2020, 9(8), 658; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080658 - 15 Aug 2020
Cited by 21 | Viewed by 5586
Abstract
Classical swine fever (CSF) is a highly contagious viral disease of pigs, including wild boar. It is regarded as one of the major problems in the pig industry as it is still endemic in many regions of the world and has the potential [...] Read more.
Classical swine fever (CSF) is a highly contagious viral disease of pigs, including wild boar. It is regarded as one of the major problems in the pig industry as it is still endemic in many regions of the world and has the potential to cause devastating epidemics, particularly in countries free of the disease. Rapid and reliable diagnosis is of utmost importance in the control of CSF. Since clinical presentations of CSF are highly variable and may be confused with other viral diseases in pigs, laboratory diagnosis is indispensable for an unambiguous diagnosis. On an international level, well-established diagnostic tests of CSF such as virus isolation, fluorescent antibody test (FAT), antigen capture antibody enzyme-linked immunosorbent assay (ELISA), reverse-transcription polymerase chain reaction (RT-PCR), virus neutralization test (VNT), and antibody ELISA have been described in detail in the OIE Terrestrial Manual. However, improved CSF diagnostic methods or alternatives based on modern technologies have been developed in recent years. This review thus presents recent advances in the diagnosis of CSF and future perspectives. Full article
(This article belongs to the Special Issue Classical Swine Fever)
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19 pages, 634 KiB  
Review
Factoring in the Complexity of the Cystic Fibrosis Lung to Understand Aspergillus fumigatus and Pseudomonas aeruginosa Interactions
by Emily Beswick, Jorge Amich and Sara Gago
Pathogens 2020, 9(8), 639; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080639 - 6 Aug 2020
Cited by 14 | Viewed by 5701
Abstract
Pseudomonas aeruginosa has long been established as the most prevalent respiratory pathogen in Cystic Fibrosis (CF) patients, with opportunistic infection causing profound morbidity and mortality. Recently, Aspergillus fumigatus has also been recognised as a key contributor to CF lung deterioration, being consistently associated [...] Read more.
Pseudomonas aeruginosa has long been established as the most prevalent respiratory pathogen in Cystic Fibrosis (CF) patients, with opportunistic infection causing profound morbidity and mortality. Recently, Aspergillus fumigatus has also been recognised as a key contributor to CF lung deterioration, being consistently associated with decreased lung function and worsened prognosis in these patients. As clinical evidence for the common occurrence of combined infection with these two pathogens increases, research into the mechanism and consequences of their interaction is becoming more relevant. Clinical evidence suggests a synergistic effect of combined infection, which translates into a poorer prognosis for the patients. In vitro results from the laboratory have identified a variety of possible synergistic and antagonistic interactions between A. fumigatus and P. aeruginosa. Here, we present a comprehensive overview of the complex environment of the CF lung and discuss how it needs to be considered to determine the exact molecular interactions that A. fumigatus and P. aeruginosa undergo during combined infection and their effects on the host. Full article
(This article belongs to the Special Issue Aspergillosis)
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21 pages, 1187 KiB  
Review
Mycoplasma bovis Infections—Occurrence, Diagnosis and Control
by Katarzyna Dudek, Robin A. J. Nicholas, Ewelina Szacawa and Dariusz Bednarek
Pathogens 2020, 9(8), 640; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080640 - 6 Aug 2020
Cited by 44 | Viewed by 8650
Abstract
Mycoplasma bovis is a cause of bronchopneumonia, mastitis and arthritis but may also affect other main organs in cattle such us the eye, ear or brain. Despite its non-zoonotic character, M. bovis infections are responsible for substantial economic health and welfare problems worldwide. [...] Read more.
Mycoplasma bovis is a cause of bronchopneumonia, mastitis and arthritis but may also affect other main organs in cattle such us the eye, ear or brain. Despite its non-zoonotic character, M. bovis infections are responsible for substantial economic health and welfare problems worldwide. M. bovis has spread worldwide, including to countries for a long time considered free of the pathogen. Control of M. bovis infections is hampered by a lack of effective vaccines and treatments due to increasing trends in antimicrobial resistance. This review summarizes the latest data on the epizootic situation of M. bovis infections and new sources/routes of transmission of the infection, and discusses the progress in diagnostics. The review includes various recommendations and suggestions which could be applied to infection control programs. Full article
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24 pages, 432 KiB  
Review
Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research
by Elisa Rampacci, Valentina Stefanetti, Fabrizio Passamonti and Marcela Henao-Tamayo
Pathogens 2020, 9(8), 641; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080641 - 6 Aug 2020
Cited by 14 | Viewed by 4313
Abstract
Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much [...] Read more.
Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much so that the incidence of NTM infections has surpassed that of Mycobacterium tuberculosis in developed countries. As a result, a growing body of the literature has focused attention on the critical role that drug susceptibility tests and infection models play in the design of appropriate therapeutic strategies against NTM diseases. This paper is an overview of the in vitro and in vivo models of NTM infection employed in the preclinical phase for early drug discovery and vaccine development. It summarizes alternative methods, not fully explored, for the characterization of anti-mycobacterial compounds. Full article
(This article belongs to the Section Vaccines and Therapeutic Developments)
23 pages, 10380 KiB  
Review
Comparative Pathology of Pseudorabies in Different Naturally and Experimentally Infected Species—A Review
by Julia Sehl and Jens Peter Teifke
Pathogens 2020, 9(8), 633; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080633 - 4 Aug 2020
Cited by 39 | Viewed by 10851
Abstract
The pseudorabies virus (PRV) is an alphaherpesvirus and the causative agent of Aujeszky’s disease (AD). PRV infects a wide range of animal species including swine as the natural host as well as ruminants, carnivores, rodents and lagomorphs. In these species, except for the [...] Read more.
The pseudorabies virus (PRV) is an alphaherpesvirus and the causative agent of Aujeszky’s disease (AD). PRV infects a wide range of animal species including swine as the natural host as well as ruminants, carnivores, rodents and lagomorphs. In these species, except for the pig, PRV infection causes acute, severe disease, characterized by insatiable itching, and is always lethal. Horses, chickens and non-human primates have been shown to be largely resistant to PRV infection, while disease in humans is still controversial. PRV is a pantropic virus, which preferably invades neural tissue, but also infects epithelia of various organs, whereupon multisystemic lesions may result. Although AD is mainly associated with severe pruritus, also known as “mad itch”, there are notable differences regarding infection route, clinical signs, viral distribution and lesion patterns in different animal species. In this comprehensive review, we will present clinico-pathologic findings from different species, which have been either shown to be susceptible to PRV infection or have been tested experimentally. Full article
(This article belongs to the Special Issue Pseudorabies Virus Infections)
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24 pages, 2145 KiB  
Review
Ticks and Tick-Borne Diseases in Cuba, Half a Century of Scientific Research
by Dasiel Obregón Alvarez, Belkis Corona-González, Alina Rodríguez-Mallón, Islay Rodríguez Gonzalez, Pastor Alfonso, Angel A. Noda Ramos, Adrian A. Díaz-Sánchez, Maylin González Navarrete, Rafmary Rodríguez Fernández, Luis Méndez Mellor, Helen N. Catanese, Manuel Peláez, Yousmel Alemán Gainza, Roxana Marrero-Perera, Lisset Roblejo-Arias, Evelyn Lobo-Rivero, Claudia B. Silva, Adivaldo H. Fonseca, Eugenio Roque López and Alejandro Cabezas-Cruz
Pathogens 2020, 9(8), 616; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080616 - 28 Jul 2020
Cited by 16 | Viewed by 6113
Abstract
Ticks and the vast array of pathogens they transmit, including bacteria, viruses, protozoa, and helminths, constitute a growing burden for human and animal health worldwide. In Cuba, the major tropical island in the Caribbean, ticks are an important cause of vector-borne diseases affecting [...] Read more.
Ticks and the vast array of pathogens they transmit, including bacteria, viruses, protozoa, and helminths, constitute a growing burden for human and animal health worldwide. In Cuba, the major tropical island in the Caribbean, ticks are an important cause of vector-borne diseases affecting livestock production, pet animal health and, to a lesser extent, human health. The higher number of tick species in the country belong to the Argasidae family and, probably less known, is the presence of an autochthonous tick species in the island, Ixodes capromydis. Herein, we provide a comprehensive review of the ticks and tick-borne pathogens (TBPs) affecting animal and human health in Cuba. The review covers research results including ecophysiology of ticks, the epidemiology of TBPs, and the diagnostic tools used currently in the country for the surveillance of TBPs. We also introduce the programs implemented in the country for tick control and the biotechnology research applied to the development of anti-tick vaccines. Full article
(This article belongs to the Collection Advances in Tick Research)
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22 pages, 1392 KiB  
Review
Modulation of Host Lipid Pathways by Pathogenic Intracellular Bacteria
by Paige E. Allen and Juan J. Martinez
Pathogens 2020, 9(8), 614; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080614 - 28 Jul 2020
Cited by 14 | Viewed by 3945
Abstract
Lipids are a broad group of molecules required for cell maintenance and homeostasis. Various intracellular pathogens have developed mechanisms of modulating and sequestering host lipid processes for a large array of functions for both bacterial and host cell survival. Among the host cell [...] Read more.
Lipids are a broad group of molecules required for cell maintenance and homeostasis. Various intracellular pathogens have developed mechanisms of modulating and sequestering host lipid processes for a large array of functions for both bacterial and host cell survival. Among the host cell lipid functions that intracellular bacteria exploit for infection are the modulation of host plasma membrane microdomains (lipid rafts) required for efficient bacterial entry; the recruitment of specific lipids for membrane integrity of intracellular vacuoles; and the utilization of host lipid droplets for the regulation of immune responses and for energy production through fatty acid β-oxidation and oxidative phosphorylation. The majority of published studies on the utilization of these host lipid pathways during infection have focused on intracellular bacterial pathogens that reside within a vacuole during infection and, thus, have vastly different requirements for host lipid metabolites when compared to those intracellular pathogens that are released into the host cytosol upon infection. Here we summarize the mechanisms by which intracellular bacteria sequester host lipid species and compare the modulation of host lipid pathways and metabolites during host cell infection by intracellular pathogens residing in either a vacuole or within the cytosol of infected mammalian cells. This review will also highlight common and unique host pathways necessary for intracellular bacterial growth that could potentially be targeted for therapeutic intervention. Full article
(This article belongs to the Special Issue Virulence Mechanisms of Rickettsiae)
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20 pages, 580 KiB  
Review
Zebrafish as a Model for Fish Diseases in Aquaculture
by Louise von Gersdorff Jørgensen
Pathogens 2020, 9(8), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9080609 - 27 Jul 2020
Cited by 38 | Viewed by 4829
Abstract
The use of zebrafish as a model for human conditions is widely recognized. Within the last couple of decades, the zebrafish has furthermore increasingly been utilized as a model for diseases in aquacultured fish species. The unique tools available in zebrafish present advantages [...] Read more.
The use of zebrafish as a model for human conditions is widely recognized. Within the last couple of decades, the zebrafish has furthermore increasingly been utilized as a model for diseases in aquacultured fish species. The unique tools available in zebrafish present advantages compared to other animal models and unprecedented in vivo imaging and the use of transgenic zebrafish lines have contributed with novel knowledge to this field. In this review, investigations conducted in zebrafish on economically important diseases in aquacultured fish species are included. Studies are summarized on bacterial, viral and parasitic diseases and described in relation to prophylactic approaches, immunology and infection biology. Considerable attention has been assigned to innate and adaptive immunological responses. Finally, advantages and drawbacks of using the zebrafish as a model for aquacultured fish species are discussed. Full article
(This article belongs to the Special Issue Fish Parasites and Immunology)
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9 pages, 433 KiB  
Review
Understanding HCMV Latency Using Unbiased Proteomic Analyses
by Emma Poole and John Sinclair
Pathogens 2020, 9(7), 590; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070590 - 20 Jul 2020
Cited by 12 | Viewed by 3034
Abstract
Human cytomegalovirus (HCMV) establishes either a latent (non-productive) or lytic (productive) infection depending upon cell type, cytokine milieu and the differentiation status of the infected cell. Undifferentiated cells, such as precursor cells of the myeloid lineage, support a latent infection whereas terminally differentiated [...] Read more.
Human cytomegalovirus (HCMV) establishes either a latent (non-productive) or lytic (productive) infection depending upon cell type, cytokine milieu and the differentiation status of the infected cell. Undifferentiated cells, such as precursor cells of the myeloid lineage, support a latent infection whereas terminally differentiated cells, such as monocytes or dendritic cells are an environment conducive to reactivation and support a lytic infection. The mechanisms which regulate HCMV in either a latent or lytic infection have been the focus of intense investigation with a view to developing novel treatments for HCMV-associated disease which can have a heavy clinical burden after reactivation or primary infection in, especially, the immune compromised. To this end, a number of studies have been carried out in an unbiased manner to address global changes occurring within the latently infected cell to address the molecular changes associated with HCMV latency. In this review, we will concentrate on the proteomic analyses which have been carried out in undifferentiated myeloid cells which either stably express specific viral latency associated genes in isolation or on cells which have been latently infected with virus. Full article
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection and Latency)
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51 pages, 2593 KiB  
Review
West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and “One Health” Implications
by Gervais Habarugira, Willy W. Suen, Jody Hobson-Peters, Roy A. Hall and Helle Bielefeldt-Ohmann
Pathogens 2020, 9(7), 589; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070589 - 19 Jul 2020
Cited by 73 | Viewed by 13630
Abstract
West Nile virus (WNV) is an important zoonotic flavivirus responsible for mild fever to severe, lethal neuroinvasive disease in humans, horses, birds, and other wildlife species. Since its discovery, WNV has caused multiple human and animal disease outbreaks in all continents, except Antarctica. [...] Read more.
West Nile virus (WNV) is an important zoonotic flavivirus responsible for mild fever to severe, lethal neuroinvasive disease in humans, horses, birds, and other wildlife species. Since its discovery, WNV has caused multiple human and animal disease outbreaks in all continents, except Antarctica. Infections are associated with economic losses, mainly due to the cost of treatment of infected patients, control programmes, and loss of animals and animal products. The pathogenesis of WNV has been extensively investigated in natural hosts as well as in several animal models, including rodents, lagomorphs, birds, and reptiles. However, most of the proposed pathogenesis hypotheses remain contentious, and much remains to be elucidated. At the same time, the unavailability of specific antiviral treatment or effective and safe vaccines contribute to the perpetuation of the disease and regular occurrence of outbreaks in both endemic and non-endemic areas. Moreover, globalisation and climate change are also important drivers of the emergence and re-emergence of the virus and disease. Here, we give an update of the pathobiology, epidemiology, diagnostics, control, and “One Health” implications of WNV infection and disease. Full article
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15 pages, 1009 KiB  
Review
Microbial Etiology and Prevention of Dental Caries: Exploiting Natural Products to Inhibit Cariogenic Biofilms
by Xiuqin Chen, Eric Banan-Mwine Daliri, Namhyeon Kim, Jong-Rae Kim, Daesang Yoo and Deog-Hwan Oh
Pathogens 2020, 9(7), 569; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070569 - 14 Jul 2020
Cited by 114 | Viewed by 15045
Abstract
Dental caries is one of the most common microbe-mediated oral diseases in human beings. At present, the accepted etiology of caries is based on a four-factor theory that includes oral microorganisms, oral environment, host, and time. Excessive exposure to dietary carbohydrates leads to [...] Read more.
Dental caries is one of the most common microbe-mediated oral diseases in human beings. At present, the accepted etiology of caries is based on a four-factor theory that includes oral microorganisms, oral environment, host, and time. Excessive exposure to dietary carbohydrates leads to the accumulation of acid-producing and acid-resistant microorganisms in the mouth. Dental caries is driven by dysbiosis of the dental biofilm adherent to the enamel surface. Effective preventive methods include inhibiting the cariogenic microorganisms, treatment with an anti-biofilm agent, and sugar intake control. The goal is to reduce the total amount of biofilm or the levels of specific pathogens. Natural products could be recommended for preventing dental caries, since they may possess fewer side effects in comparison with synthetic antimicrobials. Herein, the mechanisms of oral microbial community development and functional specialization are discussed. We highlight the application of widely explored natural products in the last five years for their ability to inhibit cariogenic microorganisms. Full article
(This article belongs to the Special Issue Microbial Interactions during Infection)
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14 pages, 1691 KiB  
Review
Mosquito Mycobiota: An Overview of Non-Entomopathogenic Fungal Interactions
by Simon Malassigné, Claire Valiente Moro and Patricia Luis
Pathogens 2020, 9(7), 564; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070564 - 12 Jul 2020
Cited by 20 | Viewed by 9447
Abstract
The growing expansion of mosquito vectors leads to the emergence of vector-borne diseases in new geographic areas and causes major public health concerns. In the absence of effective preventive treatments against most pathogens transmitted, vector control remains one of the most suitable strategies [...] Read more.
The growing expansion of mosquito vectors leads to the emergence of vector-borne diseases in new geographic areas and causes major public health concerns. In the absence of effective preventive treatments against most pathogens transmitted, vector control remains one of the most suitable strategies to prevent mosquito-borne diseases. Insecticide overuse raises mosquito resistance and deleterious impacts on the environment and non-target species. Growing knowledge of mosquito biology has allowed the development of alternative control methods. Following the concept of holobiont, mosquito-microbiota interactions play an important role in mosquito biology. Associated microbiota is known to influence many aspects of mosquito biology such as development, survival, immunity or even vector competence. Mosquito-associated microbiota is composed of bacteria, fungi, protists, viruses and nematodes. While an increasing number of studies have focused on bacteria, other microbial partners like fungi have been largely neglected despite their huge diversity. A better knowledge of mosquito-mycobiota interactions offers new opportunities to develop innovative mosquito control strategies. Here, we review the recent advances concerning the impact of mosquito-associated fungi, and particularly nonpathogenic fungi, on life-history traits (development, survival, reproduction), vector competence and behavior of mosquitoes by focusing on Culex, Aedes and Anopheles species. Full article
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34 pages, 2525 KiB  
Review
Species, Sequence Types and Alleles: Dissecting Genetic Variation in Acanthamoeba
by Paul A. Fuerst and Gregory C. Booton
Pathogens 2020, 9(7), 534; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070534 - 2 Jul 2020
Cited by 26 | Viewed by 3021
Abstract
Species designations within Acanthamoeba are problematic because of pleomorphic morphology. Molecular approaches, including DNA sequencing, hinted at a resolution that has yet to be fully achieved. Alternative approaches were required. In 1996, the Byers/Fuerst lab introduced the concept of sequence types. Differences between [...] Read more.
Species designations within Acanthamoeba are problematic because of pleomorphic morphology. Molecular approaches, including DNA sequencing, hinted at a resolution that has yet to be fully achieved. Alternative approaches were required. In 1996, the Byers/Fuerst lab introduced the concept of sequence types. Differences between isolates of Acanthamoeba could be quantitatively assessed by comparing sequences of the nuclear 18S rRNA gene, ultimately producing 22 sequence types, designated T1 through T22. The concept of sequence types helps our understanding of Acanthamoeba evolution. Nevertheless, substantial variation in the 18S rRNA gene differentiates many isolates within each sequence type. Because the majority of isolates with sequences in the international DNA databases have been studied for only a small segment of the gene, designated ASA.S1, genetic variation within this hypervariable region of the 18S rRNA gene has been scrutinized. In 2002, we first categorized variation in this region in a sample of T3 and T4 isolates from Hong Kong, observing ten “alleles” within type T4 and five “alleles” within T3. Subsequently, confusion occurred when different labs applied redundant numerical labels to identify different alleles. A more unified approach was required. We have tabulated alleles occurring in the sequences submitted to the international DNA databases, and determined their frequencies. Over 150 alleles have occurred more than once within 3500+ isolates of sequence type T4. Results from smaller samples of other sequence types (T3, T5, T11 and T15, and supergroup T2/6) have also been obtained. Our results provide new insights into the evolutionary history of Acanthamoeba, further illuminating the degree of genetic separation between significant taxonomic units within the genus, perhaps eventually elucidating what constitutes a species of Acanthamoeba. Full article
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27 pages, 679 KiB  
Review
Evidence for SARS-CoV-2 Infection of Animal Hosts
by Ahmed S. Abdel-Moneim and Elsayed M. Abdelwhab
Pathogens 2020, 9(7), 529; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070529 - 30 Jun 2020
Cited by 148 | Viewed by 19266
Abstract
COVID-19 is the first known pandemic caused by a coronavirus, SARS-CoV-2, which is the third virus in the family Coronaviridae to cause fatal infections in humans after SARS-CoV and MERS-CoV. Animals are involved in the COVID-19 pandemic. This review summarizes the role of [...] Read more.
COVID-19 is the first known pandemic caused by a coronavirus, SARS-CoV-2, which is the third virus in the family Coronaviridae to cause fatal infections in humans after SARS-CoV and MERS-CoV. Animals are involved in the COVID-19 pandemic. This review summarizes the role of animals as reservoirs, natural hosts and experimental models. SARS-CoV-2 originated from animal reservoir, most likely bats and/or pangolins. Anthroponotic transmission has been reported in cats, dogs, tigers, lions and minks. As of now, there is no a strong evidence for natural animal-to-human transmission or sustained animal-to-animal transmission of SARS-CoV-2. Experimental infections conducted by several research groups have shown that monkeys, hamsters, ferrets, cats, tree shrews, transgenic mice and fruit bats were permissive, while dogs, pigs and poultry were resistant. There is an urgent need to understand the zoonotic potential of different viruses in animals, particularly in bats, before they transmit to humans. Vaccines or antivirals against SARS-CoV-2 should be evaluated not only for humans, but also for the protection of companion animals (particularly cats) and susceptible zoo and farm animals. Full article
(This article belongs to the Section Animal Pathogens)
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55 pages, 2424 KiB  
Review
Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review
by András Fodor, Birhan Addisie Abate, Péter Deák, László Fodor, Ervin Gyenge, Michael G. Klein, Zsuzsanna Koncz, Josephat Muvevi, László Ötvös, Gyöngyi Székely, Dávid Vozik and László Makrai
Pathogens 2020, 9(7), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070522 - 29 Jun 2020
Cited by 41 | Viewed by 7222
Abstract
Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic [...] Read more.
Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic resistance often reduces fitness, but compensatory mutations may counteract this tendency. The appearance of new antibiotic resistance is frequently accompanied by a collateral sensitivity to other resistances. Organisms with an expanding open pan-genome, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, can withstand an increased number of resistances by exploiting their evolutionary plasticity and disseminating clonally or poly-clonally. Multidrug-resistant pathogen clones can become predominant under antibiotic stress conditions but, under the influence of negative frequency-dependent selection, are prevented from rising to dominance in a population in a commensal niche. Antimicrobial peptides have a great potential to combat multidrug resistance, since antibiotic-resistant bacteria have shown a high frequency of collateral sensitivity to antimicrobial peptides. In addition, the mobility patterns of antibiotic resistance, and antimicrobial peptide resistance, genes are completely different. The integron trade in commensal niches is fortunately limited by the species-specificity of resistance genes. Hence, we theorize that the suggested post-antibiotic era has not yet come, and indeed might never come. Full article
(This article belongs to the Special Issue Biological Control of Plant Diseases)
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30 pages, 2251 KiB  
Review
Coronavirus Disease Pandemic (COVID-19): Challenges and a Global Perspective
by Yashpal Singh Malik, Naveen Kumar, Shubhankar Sircar, Rahul Kaushik, Sudipta Bhat, Kuldeep Dhama, Parakriti Gupta, Kapil Goyal, Mini P Singh, Ujjala Ghoshal, Mohamed E. El Zowalaty, VinodhKumar O. R, Mohd Iqbal Yatoo, Ruchi Tiwari, Mamta Pathak, Shailesh Kumar Patel, Ranjit Sah, Alfonso J Rodriguez-Morales, Balasubramanian Ganesh, Prashant Kumar and Raj Kumar Singh add Show full author list remove Hide full author list
Pathogens 2020, 9(7), 519; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9070519 - 28 Jun 2020
Cited by 97 | Viewed by 16498
Abstract
The technology-driven world of the 21st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million [...] Read more.
The technology-driven world of the 21st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2’) within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures. Full article
(This article belongs to the Collection SARS-CoV Infections)
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18 pages, 3839 KiB  
Review
Research into Neospora caninum—What Have We Learnt in the Last Thirty Years?
by Michael P. Reichel, Lloyd C. Wahl and John T. Ellis
Pathogens 2020, 9(6), 505; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060505 - 23 Jun 2020
Cited by 19 | Viewed by 5815
Abstract
Background: Neospora caninum has been recognised world-wide, first as a disease of dogs, then as an important cause of abortions in cattle for the past thirty years. Over that time period, there have been improvements in the diagnosis of infection and abortion, new [...] Read more.
Background: Neospora caninum has been recognised world-wide, first as a disease of dogs, then as an important cause of abortions in cattle for the past thirty years. Over that time period, there have been improvements in the diagnosis of infection and abortion, new tests have been developed and validated, and it is timely to review progress to date. Methods: Bibliometric methods were used to identify major trends and research topics present in the published literature on N. caninum. The tools used were SWIFT-Review, VOSviewer and SciMAT, along with the published papers found in the MEDLINE, Dimensions and Web of Science databases. A systematic review of the published Neospora literature (n = 2933) was also carried out via MEDLINE and systematically appraised for publications relevant to the pathogenesis, pathology and diagnosis of Neospora abortions. Results: A total of 92 publications were included in the final analysis and grouped into four main time periods. In these four different time periods, the main research themes were “dogs”, “abortion”, “seroprevalence” and “infection”. Diagnostics, including PCR, dominated the first two time periods, with an increased focus on transmission and abortions, and its risk factors in cattle. Conclusions: Longitudinal analyses indicated that the main themes were consistently investigated over the last 30 years through a wide range of studies, with evolving emphasis initially on dogs and diagnostic test development, followed by application to cattle, the identification of the risk factors leading to abortion, and in the latter time periods, an understanding of the immunity and a search for vaccines. Full article
(This article belongs to the Special Issue Neospora Caninum: Infection and Immunity)
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16 pages, 1882 KiB  
Review
Emerging Prevention and Treatment Strategies to Control COVID-19
by Vipul K. Singh, Abhishek Mishra, Shubhra Singh, Premranjan Kumar, Manisha Singh, Chinnaswamy Jagannath and Arshad Khan
Pathogens 2020, 9(6), 501; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060501 - 23 Jun 2020
Cited by 19 | Viewed by 11092
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies. Full article
(This article belongs to the Collection SARS-CoV Infections)
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19 pages, 951 KiB  
Review
Coronavirus Disease 2019 (COVID–19): A Short Review on Hematological Manifestations
by Artur Słomka, Mariusz Kowalewski and Ewa Żekanowska
Pathogens 2020, 9(6), 493; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060493 - 20 Jun 2020
Cited by 73 | Viewed by 7600
Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven [...] Read more.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven effective treatments. The present article reviews the common presenting hematological manifestations of coronavirus disease 2019 (COVID–19). Elucidating the changes in hematological parameters in SARS–CoV–2 infected patients could help to understand the pathophysiology of the disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. Full article
(This article belongs to the Collection SARS-CoV Infections)
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18 pages, 994 KiB  
Review
Epigenetic Regulation of the Human Papillomavirus Life Cycle
by Michelle Mac and Cary A. Moody
Pathogens 2020, 9(6), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060483 - 18 Jun 2020
Cited by 33 | Viewed by 9257
Abstract
Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, [...] Read more.
Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, the incidence of HPV-associated cancers remains high. In addition, no vaccine has yet been licensed for therapeutic use against pre-existing HPV infections and HPV-associated diseases. Although persistent HPV infection is the major risk factor for cancer development, additional genetic and epigenetic alterations are required for progression to the malignant phenotype. Unlike genetic mutations, the reversibility of epigenetic modifications makes epigenetic regulators ideal therapeutic targets for cancer therapy. This review article will highlight the recent advances in the understanding of epigenetic modifications associated with HPV infections, with a particular focus on the role of these epigenetic changes during different stages of the HPV life cycle that are closely associated with activation of DNA damage response pathways. Full article
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31 pages, 493 KiB  
Review
Development and Challenges in Animal Tuberculosis Vaccination
by Ana Balseiro, Jobin Thomas, Christian Gortázar and María A. Risalde
Pathogens 2020, 9(6), 472; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060472 - 15 Jun 2020
Cited by 15 | Viewed by 3729
Abstract
Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to [...] Read more.
Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to TB control programs, cattle. Nowadays, the use of BCG vaccination against TB in cattle is not permitted by European Union legislation because BCG can induce a cellular immune response producing diagnostic interference in the eradication programs based on tuberculin single and comparative intradermal tests imposed worldwide. In this review, we recall the history of TB vaccination as well as different vaccine trials and the response to vaccination in both domestic and wild animals. Promising potential inactivated vaccines are also reviewed. Research studies are mainly focused to improve vaccine efficacy, and at the same time to ensure its easy administration, safety and stability in the environment. Great challenges remain, particularly in terms of vaccine candidates and also in the acceptance of vaccination. Vaccination should be included in a strategic plan for integrated control of TB under a “one health” perspective, which also includes other measures such as improved biosafety on farms to avoid or decrease contact between domestic and wild animals or control of wildlife reservoirs to avoid overabundance that may favor infection maintenance. Full article
(This article belongs to the Special Issue Tuberculosis Epidemiology and Control in Multi-Host Systems)
48 pages, 5860 KiB  
Review
Adaptive Immunity to Dengue Virus: Slippery Slope or Solid Ground for Rational Vaccine Design?
by Lucas Wilken and Guus F. Rimmelzwaan
Pathogens 2020, 9(6), 470; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060470 - 15 Jun 2020
Cited by 10 | Viewed by 9892
Abstract
The four serotypes of dengue virus are the most widespread causes of arboviral disease, currently placing half of the human population at risk of infection. Pre-existing immunity to one dengue virus serotype can predispose to severe disease following secondary infection with a different [...] Read more.
The four serotypes of dengue virus are the most widespread causes of arboviral disease, currently placing half of the human population at risk of infection. Pre-existing immunity to one dengue virus serotype can predispose to severe disease following secondary infection with a different serotype. The phenomenon of immune enhancement has complicated vaccine development and likely explains the poor long-term safety profile of a recently licenced dengue vaccine. Therefore, alternative vaccine strategies should be considered. This review summarises studies dissecting the adaptive immune responses to dengue virus infection and (experimental) vaccination. In particular, we discuss the roles of (i) neutralising antibodies, (ii) antibodies to non-structural protein 1, and (iii) T cells in protection and pathogenesis. We also address how these findings could translate into next-generation vaccine approaches that mitigate the risk of enhanced dengue disease. Finally, we argue that the development of a safe and efficacious dengue vaccine is an attainable goal. Full article
(This article belongs to the Special Issue Current Advances in Flavivirus Research)
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15 pages, 1438 KiB  
Review
Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line
by Claire D. James, Dipon Das, Molly L. Bristol and Iain M. Morgan
Pathogens 2020, 9(6), 467; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060467 - 13 Jun 2020
Cited by 8 | Viewed by 3976
Abstract
Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the [...] Read more.
Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the cell cycle including the induction of cellular senescence, as well as boost the adaptive immune response following interferon production. Human papillomaviruses (HPV) are the causative agents in a host of human cancers including cervical and oropharyngeal; HPV are responsible for around 5% of all cancers. During infection, HPV replication activates the DDR in order to promote the viral life cycle. A striking feature of HPV-infected cells is their ability to continue to proliferate in the presence of an active DDR. Simultaneously, HPV suppress the innate immune response using a number of different mechanisms. The activation of the DDR and suppression of the innate immune response are essential for the progression of the viral life cycle. Here, we describe the mechanisms HPV use to turn on the DDR, while simultaneously suppressing the innate immune response. Pushing HPV from this fine line and tipping the balance towards activation of the innate immune response would be therapeutically beneficial. Full article
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14 pages, 628 KiB  
Review
Gut Microbiome in Psoriasis: An Updated Review
by Mariusz Sikora, Albert Stec, Magdalena Chrabaszcz, Aleksandra Knot, Anna Waskiel-Burnat, Adriana Rakowska, Malgorzata Olszewska and Lidia Rudnicka
Pathogens 2020, 9(6), 463; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060463 - 12 Jun 2020
Cited by 58 | Viewed by 5900
Abstract
(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective [...] Read more.
(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy. Full article
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9 pages, 209 KiB  
Review
The Molecular Epidemiology of Echinococcus Infections
by R. C. Andrew Thompson
Pathogens 2020, 9(6), 453; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060453 - 8 Jun 2020
Cited by 25 | Viewed by 4048
Abstract
Molecular epidemiology (ME) is the application of molecular tools to determine the causation of disease. With infectious diseases, such as echinococcosis, this applies to identifying and characterising the aetiological agents and elucidating host range. Such an approach has been very successful with the [...] Read more.
Molecular epidemiology (ME) is the application of molecular tools to determine the causation of disease. With infectious diseases, such as echinococcosis, this applies to identifying and characterising the aetiological agents and elucidating host range. Such an approach has been very successful with the causative agents of echinococcosis, species of Echinococcus, initially by providing a workable and practical taxonomy and subsequently determining transmission patterns in endemic areas. This review summarises the taxonomy and nomenclature of species of Echinococcus and provides an update on ME investigations of the ecology of Echinococcus transmission, particularly in areas where more than one species of Echinococcus is maintained in cycles of transmission that may interact. Full article
(This article belongs to the Special Issue Echinococcus)
17 pages, 1664 KiB  
Review
Parasite Cystatin: Immunomodulatory Molecule with Therapeutic Activity against Immune Mediated Disorders
by Vishal Khatri, Nikhil Chauhan and Ramaswamy Kalyanasundaram
Pathogens 2020, 9(6), 431; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060431 - 30 May 2020
Cited by 16 | Viewed by 3610
Abstract
The use of parasites or their products for treating chronic inflammation associated diseases (CIADs) has generated significant attention recently. Findings from basic and clinical research have provided valuable information on strengthening the notion that parasites’ molecules can be developed as biotherapeutic agents. Completion [...] Read more.
The use of parasites or their products for treating chronic inflammation associated diseases (CIADs) has generated significant attention recently. Findings from basic and clinical research have provided valuable information on strengthening the notion that parasites’ molecules can be developed as biotherapeutic agents. Completion of the genome, secreotome, and proteome of the parasites has provided an excellent platform for screening and identifying several host immunomodulatory molecules from the parasites and evaluate their therapeutic potential for CIADs. One of the widely studied host immunomodulatory molecules of the parasites is the cysteine protease inhibitor (cystatin), which is primarily secreted by the parasites to evade host immune responses. In this review, we have attempted to summarize the findings to date on the use of helminth parasite-derived cystatin as a therapeutic agent against CIADs. Although several studies suggest a role for alternatively activated macrophages, other regulatory cells, and immunosuppressive molecules, in this immunoregulatory activity of the parasite-derived cystatin, there is still no clear demonstration as to how cystatin induces its anti-inflammatory effect in suppressing CIADs. Full article
(This article belongs to the Section Vaccines and Therapeutic Developments)
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22 pages, 1089 KiB  
Review
A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions
by Sabari Nath Neerukonda and Upendra Katneni
Pathogens 2020, 9(6), 426; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060426 - 29 May 2020
Cited by 44 | Viewed by 9493
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials. Full article
(This article belongs to the Collection SARS-CoV Infections)
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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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050408 - 24 May 2020
Cited by 19 | Viewed by 5714
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)
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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050404 - 22 May 2020
Cited by 48 | Viewed by 8816
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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050403 - 22 May 2020
Cited by 24 | Viewed by 6616
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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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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050400 - 21 May 2020
Cited by 14 | Viewed by 7941
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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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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050389 - 19 May 2020
Cited by 14 | Viewed by 7967
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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21 pages, 3014 KiB  
Review
Pathogenomics and Management of Fusarium Diseases in Plants
by Sephra N. Rampersad
Pathogens 2020, 9(5), 340; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050340 - 1 May 2020
Cited by 63 | Viewed by 6856
Abstract
There is an urgency to supplant the heavy reliance on chemical control of Fusarium diseases in different economically important, staple food crops due to development of resistance in the pathogen population, the high cost of production to the risk-averse grower, and the concomitant [...] Read more.
There is an urgency to supplant the heavy reliance on chemical control of Fusarium diseases in different economically important, staple food crops due to development of resistance in the pathogen population, the high cost of production to the risk-averse grower, and the concomitant environmental impacts. Pathogenomics has enabled (i) the creation of genetic inventories which identify those putative genes, regulators, and effectors that are associated with virulence, pathogenicity, and primary and secondary metabolism; (ii) comparison of such genes among related pathogens; (iii) identification of potential genetic targets for chemical control; and (iv) better characterization of the complex dynamics of host–microbe interactions that lead to disease. This type of genomic data serves to inform host-induced gene silencing (HIGS) technology for targeted disruption of transcription of select genes for the control of Fusarium diseases. This review discusses the various repositories and browser access points for comparison of genomic data, the strategies for identification and selection of pathogenicity- and virulence-associated genes and effectors in different Fusarium species, HIGS and successful Fusarium disease control trials with a consideration of loss of RNAi, off-target effects, and future challenges in applying HIGS for management of Fusarium diseases. Full article
(This article belongs to the Special Issue Fusarium: Pathogenomics and Inherent Resistance)
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14 pages, 715 KiB  
Review
Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview
by Francesca Marino-Merlo, Emanuela Balestrieri, Claudia Matteucci, Antonio Mastino, Sandro Grelli and Beatrice Macchi
Pathogens 2020, 9(5), 342; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9050342 - 1 May 2020
Cited by 25 | Viewed by 4174
Abstract
The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous [...] Read more.
The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous features of the diseases caused by HTLV-1, a common topic concerning related therapeutic treatments relies on the use of antiretrovirals. This review will compare the different approaches and opinions in this matter, giving a concise overview of preclinical as well as clinical studies covering all the aspects of antiretrovirals in HTLV-1 infection. Studies will be grouped on the basis of the class of antiretroviral, putting together both pre-clinical and clinical results and generally following a chronological order. Analysis of the existing literature highlights that a number of preclinical studies clearly demonstrate that different classes of antiretrovirals, already utilized as anti-HIV agents, are actually capable to efficiently contrast HTLV-1 infection. Nevertheless, the results of most of the clinical studies are generally discouraging on the same point. In conclusion, the design of new antiretrovirals more specifically focused on HTLV-1 targets, and/or the establishment of early treatments with antiretrovirals could hopefully change the perspectives of diseases caused by HTLV-1. Full article
(This article belongs to the Special Issue HTLV-1 Disease)
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25 pages, 2278 KiB  
Review
Phenylpropanoid Pathway Engineering: An Emerging Approach towards Plant Defense
by Vivek Yadav, Zhongyuan Wang, Chunhua Wei, Aduragbemi Amo, Bilal Ahmed, Xiaozhen Yang and Xian Zhang
Pathogens 2020, 9(4), 312; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040312 - 23 Apr 2020
Cited by 211 | Viewed by 14461
Abstract
Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to [...] Read more.
Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to cell wall breaches by pathogens. The whole metabolomic pathway is a complex network regulated by multiple gene families and it exhibits refined regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. The pathway genes are involved in the production of anti-microbial compounds as well as signaling molecules. The engineering in the metabolic pathway has led to a new plant defense system of which various mechanisms have been proposed including salicylic acid and antimicrobial mediated compounds. In recent years, some key players like phenylalanine ammonia lyases (PALs) from the phenylpropanoid pathway are proposed to have broad spectrum disease resistance (BSR) without yield penalties. Now we have more evidence than ever, yet little understanding about the pathway-based genes that orchestrate rapid, coordinated induction of phenylpropanoid defenses in response to microbial attack. It is not astonishing that mutants of pathway regulator genes can show conflicting results. Therefore, precise engineering of the pathway is an interesting strategy to aim at profitably tailored plants. Here, this review portrays the current progress and challenges for phenylpropanoid pathway-based resistance from the current prospective to provide a deeper understanding. Full article
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26 pages, 4754 KiB  
Review
Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically
by Handi Dahmana and Oleg Mediannikov
Pathogens 2020, 9(4), 310; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040310 - 23 Apr 2020
Cited by 80 | Viewed by 15577
Abstract
Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such [...] Read more.
Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance. Full article
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13 pages, 866 KiB  
Review
Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19)
by Muhammad Shahid Nadeem, Mazin A. Zamzami, Hani Choudhry, Bibi Nazia Murtaza, Imran Kazmi, Habib Ahmad and Abdul Rauf Shakoori
Pathogens 2020, 9(4), 307; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040307 - 22 Apr 2020
Cited by 63 | Viewed by 16917
Abstract
The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a [...] Read more.
The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions. Full article
(This article belongs to the Section Human Pathogens)
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14 pages, 905 KiB  
Review
Effects of Mycoplasmas on the Host Cell Signaling Pathways
by Sergei N. Borchsenius, Innokentii E. Vishnyakov, Olga A. Chernova, Vladislav M. Chernov and Nikolai A. Barlev
Pathogens 2020, 9(4), 308; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040308 - 22 Apr 2020
Cited by 15 | Viewed by 5241
Abstract
Mycoplasmas are the smallest free-living organisms. Reduced sizes of their genomes put constraints on the ability of these bacteria to live autonomously and make them highly dependent on the nutrients produced by host cells. Importantly, at the organism level, mycoplasmal infections may cause [...] Read more.
Mycoplasmas are the smallest free-living organisms. Reduced sizes of their genomes put constraints on the ability of these bacteria to live autonomously and make them highly dependent on the nutrients produced by host cells. Importantly, at the organism level, mycoplasmal infections may cause pathological changes to the host, including cancer and severe immunological reactions. At the molecular level, mycoplasmas often activate the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) inflammatory response and concomitantly inhibit the p53-mediated response, which normally triggers the cell cycle and apoptosis. Thus, mycoplasmal infections may be considered as cancer-associated factors. At the same time, mycoplasmas through their membrane lipoproteins (LAMPs) along with lipoprotein derivatives (lipopeptide MALP-2, macrophage-activating lipopeptide-2) are able to modulate anti-inflammatory responses via nuclear translocation and activation of Nrf2 (the nuclear factor-E2-related anti-inflammatory transcription factor 2). Thus, interactions between mycoplasmas and host cells are multifaceted and depend on the cellular context. In this review, we summarize the current information on the role of mycoplasmas in affecting the host’s intracellular signaling mediated by the interactions between transcriptional factors p53, Nrf2, and NF-κB. A better understanding of the mechanisms underlying pathologic processes associated with reprogramming eukaryotic cells that arise during the mycoplasma-host cell interaction should facilitate the development of new therapeutic approaches to treat oncogenic and inflammatory processes. Full article
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11 pages, 1018 KiB  
Review
Novel Coronavirus: Current Understanding of Clinical Features, Diagnosis, Pathogenesis, and Treatment Options
by Mohammad Ridwane Mungroo, Naveed Ahmed Khan and Ruqaiyyah Siddiqui
Pathogens 2020, 9(4), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040297 - 17 Apr 2020
Cited by 37 | Viewed by 8890
Abstract
Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family [...] Read more.
Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family to affect humans. Symptoms of COVID-19 include fever (88%), cough (68%), vomiting (5%) and diarrhoea (3.7%), and transmission of SARS-CoV-2 is thought to occur from human to human via respiratory secretions released by the infected individuals when coughing and sneezing. COVID-19 can be detected through computed tomography scans and confirmed through molecular diagnostics tools such as polymerase chain reaction. Currently, there are no effective treatments against SARS-CoV-2, hence antiviral drugs have been used to reduce the development of respiratory complications by reducing viral load. The purpose of this review is to provide a comprehensive update on the pathogenesis, clinical aspects, diagnosis, challenges and treatment of SARS-CoV-2 infections. Full article
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20 pages, 1295 KiB  
Review
Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins
by Irene Lo Cigno, Federica Calati, Silvia Albertini and Marisa Gariglio
Pathogens 2020, 9(4), 292; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040292 - 17 Apr 2020
Cited by 38 | Viewed by 6472
Abstract
The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition [...] Read more.
The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition reactivates the host innate immune response, reversing what until then was an unresponsive cellular state suitable for viral persistence and tumorigenesis. Given that the disruption of distinct mechanisms of immune evasion is an attractive strategy for cancer therapy, the race is on to gain a better understanding of E6/E7-induced immune escape and cancer progression. Here, we review recent literature on the interplay between E6/E7 and the innate immune signaling pathways cGAS/STING/TBK1, RIG-I/MAVS/TBK1, and Toll-like receptors (TLRs). The overall emerging picture is that E6 and E7 have evolved broad-spectrum mechanisms allowing for the simultaneous depletion of multiple rather than single innate immunity effectors. The cGAS/STING/TBK1 pathway appears to be the most heavily impacted, whereas the RIG-I/MAVS/TBK1, still partially functional in HPV-transformed cells, can be activated by the powerful RIG-I agonist M8, triggering the massive production of type I and III interferons (IFNs), which potentiates chemotherapy-mediated cell killing. Overall, the identification of novel therapeutic targets to restore the innate immune response in HPV-transformed cells could transform the way HPV-associated cancers are treated. Full article
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12 pages, 248 KiB  
Review
Updated Management Guidelines for Clostridioides difficile in Paediatrics
by Margherita Gnocchi, Martina Gagliardi, Pierpacifico Gismondi, Federica Gaiani, Gian Luigi de’ Angelis and Susanna Esposito
Pathogens 2020, 9(4), 291; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040291 - 16 Apr 2020
Cited by 17 | Viewed by 3932
Abstract
Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of [...] Read more.
Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile. Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Clostridioides difficile)
15 pages, 932 KiB  
Review
The Role of Apoptin in Chicken Anemia Virus Replication
by Cynthia Feng, Yingke Liang and Jose G. Teodoro
Pathogens 2020, 9(4), 294; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040294 - 16 Apr 2020
Cited by 10 | Viewed by 4153
Abstract
Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is [...] Read more.
Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is a protein of interest in anti-tumor therapy. CAV apoptin is known to localize to different subcellular compartments in transformed and non-transformed cells, depending on the DNA damage response, and the phosphorylation of several identified threonine residues. In addition, apoptin interacts with molecular machinery such as the anaphase promoting complex/cyclosome (APC/C) to inhibit the cell cycle and induce arrest in G2/M phase. While these functions of apoptin contribute to the tumor-selective effect of the protein, they also provide an important fundamental framework to apoptin’s role in viral infection, pathogenesis, and propagation. Here, we reviewed how the regulation, localization, and functions of apoptin contribute to the viral life cycle and postulated its importance in efficient replication of CAV. A model of the molecular biology of infection is critical to informing our understanding of CAV and other related animal viruses that threaten the agricultural industry. Full article
(This article belongs to the Special Issue Chicken Anaemia Virus Infection)
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23 pages, 487 KiB  
Review
Legionella pneumophila and Protozoan Hosts: Implications for the Control of Hospital and Potable Water Systems
by Muhammad Atif Nisar, Kirstin E. Ross, Melissa H. Brown, Richard Bentham and Harriet Whiley
Pathogens 2020, 9(4), 286; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040286 - 15 Apr 2020
Cited by 28 | Viewed by 4139
Abstract
Legionella pneumophila is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires’ disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This [...] Read more.
Legionella pneumophila is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires’ disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This review collates the literature describing interactions between L. pneumophila and protozoan hosts in hospital and municipal potable water distribution systems. The effectiveness of currently available water disinfection protocols to control L. pneumophila and its protozoan hosts is explored. The studies identified in this systematic literature review demonstrated the failure of common disinfection procedures to achieve long term elimination of L. pneumophila and protozoan hosts from potable water. It has been demonstrated that protozoan hosts facilitate the intracellular replication and packaging of viable L. pneumophila in infectious vesicles; whereas, cyst-forming protozoans provide protection from prolonged environmental stress. Disinfection procedures and protozoan hosts also facilitate biogenesis of viable but non-culturable (VBNC) L. pneumophila which have been shown to be highly resistant to many water disinfection protocols. In conclusion, a better understanding of L. pneumophila-protozoan interactions and the structure of complex microbial biofilms is required for the improved management of L. pneumophila and the prevention of LD. Full article
(This article belongs to the Special Issue Legionella Contamination in Water Environment)
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17 pages, 1185 KiB  
Review
The Role of Long Noncoding RNAs in Human Papillomavirus-associated Pathogenesis
by Surendra Sharma and Karl Munger
Pathogens 2020, 9(4), 289; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040289 - 15 Apr 2020
Cited by 22 | Viewed by 5883
Abstract
Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack [...] Read more.
Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack intrinsic enzymatic activities and they function by binding to cellular regulatory molecules, thereby subverting normal cellular homeostasis. Much effort has focused on identifying protein targets of the E6 and E7 proteins, but it has been estimated that ~98% of the human transcriptome does not encode proteins. There is a growing interest in studying noncoding RNAs as biochemical targets and biological mediators of human papillomavirus (HPV) E6/E7 oncogenic activities. This review focuses on HPV E6/E7 targeting cellular long noncoding RNAs, a class of biologically versatile molecules that regulate almost every known biological process and how this may contribute to viral oncogenesis. Full article
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15 pages, 1281 KiB  
Review
A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population
by Jacob Dag Berild, Brita Askeland Winje, Didrik Frimann Vestrheim, Hans-Christian Slotved, Palle Valentiner-Branth, Adam Roth and Jann Storsäter
Pathogens 2020, 9(4), 259; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040259 - 3 Apr 2020
Cited by 29 | Viewed by 5491
Abstract
Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the [...] Read more.
Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle–Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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28 pages, 1972 KiB  
Review
The Neuropathic Itch Caused by Pseudorabies Virus
by Kathlyn Laval and Lynn W. Enquist
Pathogens 2020, 9(4), 254; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9040254 - 31 Mar 2020
Cited by 52 | Viewed by 8402
Abstract
Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it [...] Read more.
Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it can establish a quiescent, latent infection. While the natural host of PRV is the swine, a broad spectrum of mammals, including rodents, cats, dogs, and cattle can be infected. Since the nineteenth century, PRV infection is known to cause a severe acute neuropathy, the so called “mad itch” in non-natural hosts, but surprisingly not in swine. In the past, most scientific efforts have been directed to eradicating PRV from pig farms by the use of effective marker vaccines, but little attention has been given to the processes leading to the mad itch. The main objective of this review is to provide state-of-the-art information on the mechanisms governing PRV-induced neuropathic itch in non-natural hosts. We highlight similarities and key differences in the pathogenesis of PRV infections between non-natural hosts and pigs that might explain their distinctive clinical outcomes. Current knowledge on the neurobiology and possible explanations for the unstoppable itch experienced by PRV-infected animals is also reviewed. We summarize recent findings concerning PRV-induced neuroinflammatory responses in mice and address the relevance of this animal model to study other alphaherpesvirus-induced neuropathies, such as those observed for VZV infection. Full article
(This article belongs to the Special Issue Pseudorabies Virus Infections)
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21 pages, 2582 KiB  
Review
The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis
by Aude Cerutti, Nicolas Blanchard and Sébastien Besteiro
Pathogens 2020, 9(3), 234; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9030234 - 21 Mar 2020
Cited by 50 | Viewed by 13537
Abstract
Toxoplasma gondii is a ubiquitous parasitic protist found in a wide variety of hosts, including a large proportion of the human population. Beyond an acute phase which is generally self-limited in immunocompetent individuals, the ability of the parasite to persist as a dormant [...] Read more.
Toxoplasma gondii is a ubiquitous parasitic protist found in a wide variety of hosts, including a large proportion of the human population. Beyond an acute phase which is generally self-limited in immunocompetent individuals, the ability of the parasite to persist as a dormant stage, called bradyzoite, is an important aspect of toxoplasmosis. Not only is this stage not eliminated by current treatments, but it can also reactivate in immunocompromised hosts, leading to a potentially fatal outcome. Yet, despite its critical role in the pathology, the bradyzoite stage is relatively understudied. One main explanation is that it is a considerably challenging model, which essentially has to be derived from in vivo sources. However, recent progress on genetic manipulation and in vitro differentiation models now offers interesting perspectives for tackling key biological questions related to this particularly important developmental stage. Full article
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14 pages, 3323 KiB  
Review
SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far
by Firas A. Rabi, Mazhar S. Al Zoubi, Ghena A. Kasasbeh, Dunia M. Salameh and Amjad D. Al-Nasser
Pathogens 2020, 9(3), 231; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9030231 - 20 Mar 2020
Cited by 484 | Viewed by 141999
Abstract
In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and [...] Read more.
In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes. Full article
(This article belongs to the Collection SARS-CoV Infections)
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