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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14 pages, 782 KiB  
Review
Comparing the Folds of Prions and Other Pathogenic Amyloids
by José Miguel Flores-Fernández, Vineet Rathod and Holger Wille
Pathogens 2018, 7(2), 50; https://doi.org/10.3390/pathogens7020050 - 4 May 2018
Cited by 10 | Viewed by 6581
Abstract
Pathogenic amyloids are the main feature of several neurodegenerative disorders, such as Creutzfeldt–Jakob disease, Alzheimer’s disease, and Parkinson’s disease. High resolution structures of tau paired helical filaments (PHFs), amyloid-β(1-42) (Aβ(1-42)) fibrils, and α-synuclein fibrils were recently reported using cryo-electron microscopy. A high-resolution structure [...] Read more.
Pathogenic amyloids are the main feature of several neurodegenerative disorders, such as Creutzfeldt–Jakob disease, Alzheimer’s disease, and Parkinson’s disease. High resolution structures of tau paired helical filaments (PHFs), amyloid-β(1-42) (Aβ(1-42)) fibrils, and α-synuclein fibrils were recently reported using cryo-electron microscopy. A high-resolution structure for the infectious prion protein, PrPSc, is not yet available due to its insolubility and its propensity to aggregate, but cryo-electron microscopy, X-ray fiber diffraction, and other approaches have defined the overall architecture of PrPSc as a 4-rung β-solenoid. Thus, the structure of PrPSc must have a high similarity to that of the fungal prion HET-s, which is part of the fungal heterokaryon incompatibility system and contains a 2-rung β-solenoid. This review compares the structures of tau PHFs, Aβ(1-42), and α-synuclein fibrils, where the β-strands of each molecule stack on top of each other in a parallel in-register arrangement, with the β-solenoid folds of HET-s and PrPSc. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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14 pages, 240 KiB  
Review
Molecular Responses to the Zika Virus in Mosquitoes
by Catalina Alfonso-Parra and Frank W. Avila
Pathogens 2018, 7(2), 49; https://doi.org/10.3390/pathogens7020049 - 3 May 2018
Cited by 14 | Viewed by 4464
Abstract
The Zika virus (ZIKV), originally discovered in 1947, did not become a major concern until the virus swept across the Pacific and into the Americas in the last decade, bringing with it news of neurological complications and birth defects in ZIKV affected areas. [...] Read more.
The Zika virus (ZIKV), originally discovered in 1947, did not become a major concern until the virus swept across the Pacific and into the Americas in the last decade, bringing with it news of neurological complications and birth defects in ZIKV affected areas. This prompted researchers to dissect the molecular interactions between ZIKV and the mosquito vector in an attempt to better understand not only the changes that occur upon infection, but to also identify molecules that may potentially enhance or suppress a mosquito’s ability to become infected and/or transmit the virus. Here, we review what is currently known regarding ZIKV-mosquito molecular interactions, focusing on ZIKV infection of Aedes aegypti and Aedes albopictus, the primary species implicated in transmitting ZIKV during the recent outbreaks. Full article
(This article belongs to the Special Issue Virus-Host Interactions of Zika Virus)
15 pages, 53444 KiB  
Article
Whole Genome Classification and Phylogenetic Analyses of Rotavirus B strains from the United States
by Frances K. Shepherd, Diana Maria Herrera-Ibata, Elizabeth Porter, Nitipong Homwong, Richard Hesse, Jianfa Bai and Douglas G. Marthaler
Pathogens 2018, 7(2), 44; https://doi.org/10.3390/pathogens7020044 - 18 Apr 2018
Cited by 16 | Viewed by 7058
Abstract
Rotaviruses (RVs) are a major etiological agent of acute viral gastroenteritis in humans and young animals, with rotavirus B (RVB) often detected in suckling and weaned pigs. Group A rotavirus classification is currently based on the two outer capsid proteins, VP7 and VP4, [...] Read more.
Rotaviruses (RVs) are a major etiological agent of acute viral gastroenteritis in humans and young animals, with rotavirus B (RVB) often detected in suckling and weaned pigs. Group A rotavirus classification is currently based on the two outer capsid proteins, VP7 and VP4, and the middle layer protein, VP6. Using RVB strains generated in this study and reference sequences from GenBank, pairwise identity frequency graphs and phylogenetic trees were constructed for the eleven gene segments of RVB to estimate the nucleotide identity cutoff values for different genotypes and determine the genotype diversity per gene segment. Phylogenetic analysis of VP7, VP4, VP6, VP1–VP3, and NSP1–NSP5 identified 26G, 5P, 13I, 5R, 5C, 5M, 8A, 10N, 6T, 4E, and 7H genotypes, respectively. The analysis supports the previously proposed cutoff values for the VP7, VP6, NSP1, and NSP3 gene segments (80%, 81%, 76% and 78%, respectively) and suggests new cutoff values for the VP4, VP1, VP2, VP3, NSP2, NSP4, and NSP5 (80%, 78%, 79%, 77% 83%, 76%, and 79%, respectively). Reassortment events were detected between the porcine RVB strains from our study. This research describes the genome constellations for the complete genome of Group B rotaviruses in different host species. Full article
(This article belongs to the Special Issue Rotavirus Epidemiology: Host, Climate and Vaccine Influences)
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16 pages, 2359 KiB  
Article
Multifocal Equine Influenza Outbreak with Vaccination Breakdown in Thoroughbred Racehorses
by Sarah Gildea, Marie Garvey, Pamela Lyons, Rachel Lyons, Jacinta Gahan, Cathal Walsh and Ann Cullinane
Pathogens 2018, 7(2), 43; https://doi.org/10.3390/pathogens7020043 - 17 Apr 2018
Cited by 21 | Viewed by 4738
Abstract
Equine influenza (EI) outbreaks occurred on 19 premises in Ireland during 2014. Disease affected thoroughbred (TB) and non-TB horses/ponies on a variety of premises including four racing yards. Initial clinical signs presented on 16 premises within a two-month period. Extensive field investigations were [...] Read more.
Equine influenza (EI) outbreaks occurred on 19 premises in Ireland during 2014. Disease affected thoroughbred (TB) and non-TB horses/ponies on a variety of premises including four racing yards. Initial clinical signs presented on 16 premises within a two-month period. Extensive field investigations were undertaken, and the diagnostic effectiveness of a TaqMan RT-PCR assay was demonstrated in regularly-vaccinated and sub-clinically-affected horses. Epidemiological data and repeat clinical samples were collected from 305 horses, of which 40% were reported as clinically affected, 39% were identified as confirmed cases and 11% were sub-clinically affected. Multivariable analysis demonstrated a significant association between clinical signs and age, vaccination status and number of vaccine doses received. Vaccine breakdown was identified in 31% of horses with up to date vaccination records. This included 27 horses in four different racing yards. Genetic and antigenic analysis identified causal viruses as belonging to Clade 2 of the Florida sublineage (FCL2). At the time of this study, no commercially available EI vaccine in Ireland had been updated in line with World Organisation for Animal Health (OIE) recommendations to include a FCL2 virus. The findings of this study highlight the potential ease with which EI can spread among partially immune equine populations. Full article
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23 pages, 4273 KiB  
Review
The Microenvironment in Epstein–Barr Virus-Associated Malignancies
by Geok Wee Tan, Lydia Visser, Lu Ping Tan, Anke Van den Berg and Arjan Diepstra
Pathogens 2018, 7(2), 40; https://doi.org/10.3390/pathogens7020040 - 13 Apr 2018
Cited by 41 | Viewed by 8328
Abstract
The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an [...] Read more.
The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an aspecific reaction to the tumor cells. In fact, latent EBV-infected tumor cells utilize several specific mechanisms to form and shape the TME to their own benefit. These mechanisms have been studied largely in the context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and EBV+ gastric cancer. This review describes the composition, immune escape mechanisms, and tumor cell promoting properties of the TME in these three malignancies. Mechanisms of susceptibility which regularly involve genes related to immune system function are also discussed, as only a small proportion of EBV-infected individuals develops an EBV-associated malignancy. Full article
(This article belongs to the Special Issue Emerging Topics in Epstein-Barr virus-Associated Diseases)
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11 pages, 393 KiB  
Article
Presence of Human Enteric Viruses, Protozoa, and Indicators of Pathogens in the Bagmati River, Nepal
by Sarmila Tandukar, Jeevan B. Sherchand, Dinesh Bhandari, Samendra P. Sherchan, Bikash Malla, Rajani Ghaju Shrestha and Eiji Haramoto
Pathogens 2018, 7(2), 38; https://doi.org/10.3390/pathogens7020038 - 6 Apr 2018
Cited by 39 | Viewed by 7348
Abstract
Quantification of waterborne pathogens in water sources is essential for alerting the community about health hazards. This study determined the presence of human enteric viruses and protozoa in the Bagmati River, Nepal, and detected fecal indicator bacteria (total coliforms, Escherichia coli, and [...] Read more.
Quantification of waterborne pathogens in water sources is essential for alerting the community about health hazards. This study determined the presence of human enteric viruses and protozoa in the Bagmati River, Nepal, and detected fecal indicator bacteria (total coliforms, Escherichia coli, and Enterococcus spp.), human-fecal markers (human Bacteroidales and JC and BK polyomaviruses), and index viruses (tobacco mosaic virus and pepper mild mottle virus). During a one-year period between October 2015 and September 2016, a total of 18 surface water samples were collected periodically from three sites along the river. Using quantitative polymerase chain reaction, all eight types of human enteric viruses tested—including adenoviruses, noroviruses, and enteroviruses, were detected frequently at the midstream and downstream sites, with concentrations of 4.4–8.3 log copies/L. Enteroviruses and saliviruses were the most frequently detected enteric viruses, which were present in 72% (13/18) of the tested samples. Giardia spp. were detected by fluorescence microscopy in 78% (14/18) of the samples, with a lower detection ratio at the upstream site. Cryptosporidium spp. were detected only at the midstream and downstream sites, with a positive ratio of 39% (7/18). The high concentrations of enteric viruses suggest that the midstream and downstream regions are heavily contaminated with human feces and that there are alarming possibilities of waterborne diseases. The concentrations of enteric viruses were significantly higher in the dry season than the wet season (p < 0.05). There was a significant positive correlation between the concentrations of human enteric viruses and the tested indicators for the presence of pathogens (IPP) (p < 0.05), suggesting that these IPP can be used to estimate the presence of enteric viruses in the Bagmati River water. Full article
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45 pages, 2111 KiB  
Review
The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids
by Letícia Marchese, Janaina De Freitas Nascimento, Flávia Silva Damasceno, Frédéric Bringaud, Paul A. M. Michels and Ariel Mariano Silber
Pathogens 2018, 7(2), 36; https://doi.org/10.3390/pathogens7020036 - 1 Apr 2018
Cited by 64 | Viewed by 13732
Abstract
Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This [...] Read more.
Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This implies that during their life cycles each of them faces environments with different physical, chemical, biochemical, and biological characteristics. In this work we review how amino acids are obtained from such environments, how they are metabolized, and how they and some of their intermediate metabolites are used as a survival toolbox to cope with the different conditions in which these parasites should establish the infections in the insects and mammalian hosts. Full article
(This article belongs to the Special Issue Trypanosoma brucei)
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11 pages, 8727 KiB  
Article
Acidocalcisome-Mitochondrion Membrane Contact Sites in Trypanosoma brucei
by Srinivasan Ramakrishnan, Beejan Asady and Roberto Docampo
Pathogens 2018, 7(2), 33; https://doi.org/10.3390/pathogens7020033 - 22 Mar 2018
Cited by 27 | Viewed by 5886
Abstract
Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such [...] Read more.
Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such contact sites in Trypanosoma brucei. In mammalian cells, endoplasmic reticulum-mitochondria contact sites facilitate mitochondrial uptake of Ca2+ released by the ER-located inositol 1,4,5-trisphosphate receptor (InsP3R). However, the InsP3R in trypanosomes localizes to acidocalcisomes, which serve as major Ca2+ stores in these parasites. In this work, we have used super-resolution structured illumination microscopy and electron microscopy to identify membrane contact sites that exist between acidocalcisomes and mitochondria. Furthermore, we have confirmed the close association of these organelles using proximity ligation assays. Characterization of these contact sites may be a necessary starting point towards unraveling the role of Ca2+ in regulating trypanosome bioenergetics. Full article
(This article belongs to the Special Issue Trypanosoma brucei)
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15 pages, 2333 KiB  
Review
The Cooperative Functions of the EBNA3 Proteins Are Central to EBV Persistence and Latency
by Christine T. Styles, Kostas Paschos, Robert E. White and Paul J. Farrell
Pathogens 2018, 7(1), 31; https://doi.org/10.3390/pathogens7010031 - 17 Mar 2018
Cited by 27 | Viewed by 6811
Abstract
The Epstein–Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein–Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in [...] Read more.
The Epstein–Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein–Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in vitro B cell transformation and EBV persistence in vivo. Despite structural and sequence similarities, and evidence of substantial cooperative activity between the EBNA3 proteins, they perform quite different, often opposing functions. Both EBNA3A and EBNA3C are involved in the repression of important tumour suppressive pathways and are considered oncogenic. In contrast, EBNA3B exhibits tumour suppressive functions. This review focuses on how the EBNA3 proteins achieve the delicate balance required to support EBV persistence and latency, with emphasis on the contribution of the Allday laboratory to the field of EBNA3 biology. Full article
(This article belongs to the Special Issue Emerging Topics in Epstein-Barr virus-Associated Diseases)
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18 pages, 3090 KiB  
Review
Navigating the Host Cell Response during Entry into Sites of Latent Cytomegalovirus Infection
by Matthew J. Murray, Nicholas E. Peters and Matthew B. Reeves
Pathogens 2018, 7(1), 30; https://doi.org/10.3390/pathogens7010030 - 16 Mar 2018
Cited by 20 | Viewed by 6623
Abstract
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very [...] Read more.
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection—where the virus establishes an infection in an absence of many gene products specific for lytic infection—these initial interactions are crucial events. In this review, we will discuss key host responses triggered by viral infection and how, in turn, the virus ameliorates the impact on the establishment of non-lytic infections of cells. We will focus on strategies to evade intrinsic antiviral and innate immune responses and consider their impact on viral infection. Finally, we will consider the hypothesis that the very early events upon viral infection are important for dictating the outcome of infection and consider the possibility that events that occur during entry into non-permissive cells are unique and thus contribute to the establishment of latency. Full article
(This article belongs to the Special Issue Cytomegalovirus Infection)
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12 pages, 211 KiB  
Review
Control of Bovine Viral Diarrhea
by Volker Moennig and Paul Becher
Pathogens 2018, 7(1), 29; https://doi.org/10.3390/pathogens7010029 - 8 Mar 2018
Cited by 85 | Viewed by 9773
Abstract
Bovine viral diarrhea (BVD) is one of the most important infectious diseases of cattle with respect to animal health and economic impact. Its stealthy nature, prolonged transient infections, and the presence of persistently infected (PI) animals as efficient reservoirs were responsible for its [...] Read more.
Bovine viral diarrhea (BVD) is one of the most important infectious diseases of cattle with respect to animal health and economic impact. Its stealthy nature, prolonged transient infections, and the presence of persistently infected (PI) animals as efficient reservoirs were responsible for its ubiquitous presence in cattle populations worldwide. Whereas it was initially thought that the infection was impossible to control, effective systematic control strategies have emerged over the last 25 years. The common denominators of all successful control programs were systematic control, removal of PI animals, movement controls for infected herds, strict biosecurity, and surveillance. Scandinavian countries, Austria, and Switzerland successfully implemented these control programs without using vaccination. Vaccination as an optional and additional control tool was used by e.g., Germany, Belgium, Ireland, and Scotland. The economic benefits of BVD control programs had been assessed in different studies. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea virus)
16 pages, 918 KiB  
Review
Pharmacological Agents Targeting the Cellular Prion Protein
by Maria Letizia Barreca, Nunzio Iraci, Silvia Biggi, Violetta Cecchetti and Emiliano Biasini
Pathogens 2018, 7(1), 27; https://doi.org/10.3390/pathogens7010027 - 7 Mar 2018
Cited by 37 | Viewed by 6906
Abstract
Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates [...] Read more.
Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates in brain tissues of affected individuals. PrPSc is a self-catalytic protein assembly capable of recruiting native conformers of PrPC, and causing their rearrangement into new PrPSc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrPSc, and a number of compounds have shown potent anti-prion effects in experimental models. Unfortunately, so far, none of these molecules has successfully been translated into effective therapies for prion diseases. Moreover, mounting evidence suggests that PrPSc might be a difficult pharmacological target because of its poorly defined structure, heterogeneous composition, and ability to generate different structural conformers (known as prion strains) that can elude pharmacological intervention. In the last decade, a less intuitive strategy to overcome all these problems has emerged: targeting PrPC, the common substrate of any prion strain replication. This alternative approach possesses several technical and theoretical advantages, including the possibility of providing therapeutic effects also for other neurodegenerative disorders, based on recent observations indicating a role for PrPC in delivering neurotoxic signals of different misfolded proteins. Here, we provide an overview of compounds claimed to exert anti-prion effects by directly binding to PrPC, discussing pharmacological properties and therapeutic potentials of each chemical class. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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45 pages, 13782 KiB  
Review
EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts
by Stefan D. Dojcinov, Falko Fend and Leticia Quintanilla-Martinez
Pathogens 2018, 7(1), 28; https://doi.org/10.3390/pathogens7010028 - 7 Mar 2018
Cited by 92 | Viewed by 13192
Abstract
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders [...] Read more.
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored. Full article
(This article belongs to the Special Issue Emerging Topics in Epstein-Barr virus-Associated Diseases)
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30 pages, 15400 KiB  
Review
Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery
by Iram Khan Iqbal, Sapna Bajeli, Ajit Kumar Akela and Ashwani Kumar
Pathogens 2018, 7(1), 24; https://doi.org/10.3390/pathogens7010024 - 23 Feb 2018
Cited by 48 | Viewed by 12097
Abstract
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable [...] Read more.
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail. Full article
(This article belongs to the Special Issue Mechanisms of Mycobacterium tuberculosis Pathogenesis)
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9 pages, 204 KiB  
Opinion
Congenital Toxoplasmosis: A Plea for a Neglected Disease
by Martine Wallon and François Peyron
Pathogens 2018, 7(1), 25; https://doi.org/10.3390/pathogens7010025 - 23 Feb 2018
Cited by 60 | Viewed by 7568
Abstract
Maternal infection by Toxoplasma gondii during pregnancy may have serious consequences for the fetus, ranging from miscarriage, central nervous system involvement, retinochoroiditis, or subclinical infection at birth with a risk of late onset of ocular diseases. As infection in pregnant women is usually [...] Read more.
Maternal infection by Toxoplasma gondii during pregnancy may have serious consequences for the fetus, ranging from miscarriage, central nervous system involvement, retinochoroiditis, or subclinical infection at birth with a risk of late onset of ocular diseases. As infection in pregnant women is usually symptomless, the diagnosis relies only on serological tests. Some countries like France and Austria have organized a regular serological testing of pregnant women, some others have no prenatal program of surveillance. Reasons for these discrepant attitudes are many and debatable. Among them are the efficacy of antenatal treatment and cost-effectiveness of such a program. A significant body of data demonstrated that rapid onset of treatment after maternal infection reduces the risk and severity of fetal infection. Recent cost-effectiveness studies support regular screening. This lack of consensus put both pregnant women and care providers in a difficult situation. Another reason why congenital toxoplasmosis is disregarded in some countries is the lack of precise information about its impact on the population. Precise estimations on the burden of the disease can be achieved by systematic screening that will avoid bias or underreporting of cases and provide a clear view of its outcome. Full article
(This article belongs to the Special Issue Toxoplasma gondii Infection)
11 pages, 3347 KiB  
Review
The Structure of PrPSc Prions
by Holger Wille and Jesús R. Requena
Pathogens 2018, 7(1), 20; https://doi.org/10.3390/pathogens7010020 - 7 Feb 2018
Cited by 67 | Viewed by 20780
Abstract
PrPSc (scrapie isoform of the prion protein) prions are the infectious agent behind diseases such as Creutzfeldt–Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer), as well as goat and sheep scrapie. [...] Read more.
PrPSc (scrapie isoform of the prion protein) prions are the infectious agent behind diseases such as Creutzfeldt–Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer), as well as goat and sheep scrapie. PrPSc is an alternatively folded variant of the cellular prion protein, PrPC, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrPC is well studied, the structure of PrPSc resisted high-resolution determination due to its general insolubility and propensity to aggregate. Cryo-electron microscopy, X-ray fiber diffraction, and a variety of other approaches defined the structure of PrPSc as a four-rung β-solenoid. A high-resolution structure of PrPSc still remains to be solved, but the four-rung β-solenoid architecture provides a molecular framework for the autocatalytic propagation mechanism that gives rise to the alternative conformation of PrPSc. Here, we summarize the current knowledge regarding the structure of PrPSc and speculate about the molecular conversion mechanisms that leads from PrPC to PrPSc. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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11 pages, 5359 KiB  
Review
Pathogenesis and Animal Models of Post-Primary (Bronchogenic) Tuberculosis, A Review
by Robert L. Hunter, Jefrey K. Actor, Shen-An Hwang, Arshad Khan, Michael E. Urbanowski, Deepak Kaushal and Chinnaswamy Jagannath
Pathogens 2018, 7(1), 19; https://doi.org/10.3390/pathogens7010019 - 6 Feb 2018
Cited by 29 | Viewed by 8441
Abstract
Primary and post-primary tuberculosis (TB) are different diseases caused by the same organism. Primary TB produces systemic immunity. Post-primary TB produces cavities to support massive proliferation of organisms for transmission of infection to new hosts from a person with sufficient immunity to prevent [...] Read more.
Primary and post-primary tuberculosis (TB) are different diseases caused by the same organism. Primary TB produces systemic immunity. Post-primary TB produces cavities to support massive proliferation of organisms for transmission of infection to new hosts from a person with sufficient immunity to prevent systemic infection. Post-primary, also known as bronchogenic, TB begins in humans as asymptomatic bronchial spread of obstructive lobular pneumonia, not as expanding granulomas. Most lesions regress spontaneously. However, some undergo caseation necrosis that is coughed out through the necrotic bronchi to form cavities. Caseous pneumonia that is not expelled through the bronchi is retained to become the focus of fibrocaseous disease. No animal reproduces this entire process. However, it appears that many mammals utilize similar mechanisms, but fail to coordinate them as do humans. Understanding this makes it possible to use human tuberculous lung sections to guide manipulation of animals to produce models of particular human lesions. For example, slowly progressive and reactivation TB in mice resemble developing human bronchogenic TB. Similarly, bronchogenic TB and cavities resembling those in humans can be induced by bronchial infection of sensitized rabbits. Granulomas in guinea pigs have characteristics of both primary and post primary TB. Mice can be induced to produce a spectrum of human like caseating granulomas. There is evidence that primates can develop bronchogenic TB. We are optimistic that such models developed by coordinated study of human and animal tissues can be used with modern technologies to finally address long-standing questions about host/parasite relationships in TB, and support development of targeted therapeutics and vaccines. Full article
(This article belongs to the Special Issue Mechanisms of Mycobacterium tuberculosis Pathogenesis)
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16 pages, 787 KiB  
Review
Mycobacterium tuberculosis Molecular Determinants of Infection, Survival Strategies, and Vulnerable Targets
by Davide M. Ferraris, Riccardo Miggiano, Franca Rossi and Menico Rizzi
Pathogens 2018, 7(1), 17; https://doi.org/10.3390/pathogens7010017 - 1 Feb 2018
Cited by 33 | Viewed by 14155
Abstract
Mycobacterium tuberculosis is the causative agent of tuberculosis, an ancient disease which, still today, represents a major threat for the world population. Despite the advances in medicine and the development of effective antitubercular drugs, the cure of tuberculosis involves prolonged therapies which complicate [...] Read more.
Mycobacterium tuberculosis is the causative agent of tuberculosis, an ancient disease which, still today, represents a major threat for the world population. Despite the advances in medicine and the development of effective antitubercular drugs, the cure of tuberculosis involves prolonged therapies which complicate the compliance and monitoring of drug administration and treatment. Moreover, the only available antitubercular vaccine fails to provide an effective shield against adult lung tuberculosis, which is the most prevalent form. Hence, there is a pressing need for effective antitubercular drugs and vaccines. This review highlights recent advances in the study of selected M. tuberculosis key molecular determinants of infection and vulnerable targets whose structures could be exploited for the development of new antitubercular agents. Full article
(This article belongs to the Special Issue Mechanisms of Mycobacterium tuberculosis Pathogenesis)
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9 pages, 533 KiB  
Review
On the Demographic and Selective Forces Shaping Patterns of Human Cytomegalovirus Variation within Hosts
by Andrew M. Sackman, Susanne P. Pfeifer, Timothy F. Kowalik and Jeffrey D. Jensen
Pathogens 2018, 7(1), 16; https://doi.org/10.3390/pathogens7010016 - 28 Jan 2018
Cited by 19 | Viewed by 4997
Abstract
Human cytomegalovirus (HCMV) is a member of the β -herpesvirus subfamily within Herpesviridae that is nearly ubiquitous in human populations, and infection generally results only in mild symptoms. However, symptoms can be severe in immunonaive individuals, and transplacental congenital infection of HCMV can [...] Read more.
Human cytomegalovirus (HCMV) is a member of the β -herpesvirus subfamily within Herpesviridae that is nearly ubiquitous in human populations, and infection generally results only in mild symptoms. However, symptoms can be severe in immunonaive individuals, and transplacental congenital infection of HCMV can result in serious neurological sequelae. Recent work has revealed much about the demographic and selective forces shaping the evolution of congenitally transmitted HCMV both on the level of hosts and within host compartments, providing insight into the dynamics of congenital infection, reinfection, and evolution of HCMV with important implications for the development of effective treatments and vaccines. Full article
(This article belongs to the Special Issue Cytomegalovirus Infection)
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14 pages, 562 KiB  
Review
A Comparison of Oral and Intravenous Mouse Models of Listeriosis
by Michelle G. Pitts and Sarah E. F. D’Orazio
Pathogens 2018, 7(1), 13; https://doi.org/10.3390/pathogens7010013 - 20 Jan 2018
Cited by 17 | Viewed by 6686
Abstract
Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal [...] Read more.
Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well as the development of a foodborne route of transmission has reignited interest in studying oral models of listeriosis. In this review, we analyze previously published reports to highlight both the similarities and differences in tissue colonization and host response to infection using either oral or i.v. inoculation. Full article
(This article belongs to the Special Issue Listeria monocytogenes and Its Interactions with the Host)
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12 pages, 279 KiB  
Review
Modulation of the Fungal-Host Interaction by the Intra-Species Diversity of C. albicans
by Christina Braunsdorf and Salomé LeibundGut-Landmann
Pathogens 2018, 7(1), 11; https://doi.org/10.3390/pathogens7010011 - 17 Jan 2018
Cited by 12 | Viewed by 4531
Abstract
The incidence of human infections caused by the opportunistic fungal pathogen Candida albicans is on the rise due to increasing numbers of immunosuppressed patients. The importance of the immune system in preventing overgrowth of the colonizing fungus and thereby limiting infection is well [...] Read more.
The incidence of human infections caused by the opportunistic fungal pathogen Candida albicans is on the rise due to increasing numbers of immunosuppressed patients. The importance of the immune system in preventing overgrowth of the colonizing fungus and thereby limiting infection is well recognized and host protective mechanisms widely investigated. Only recently, it was recognized that the natural diversity in the fungal species could also influence the outcome of the interaction between the fungus and the host. C. albicans strain-specific differences are complex and their regulation at the genomic, genetic, and epigenetic level and by environmental factors is only partially understood. In this review, we provide an overview of the natural diversity of C. albicans and discuss how it impacts host-fungal interactions and thereby affects the balance between commensalism versus disease. Full article
(This article belongs to the Special Issue Pathogenesis and Virulence of Candida albicans and Candida glabrata)
17 pages, 1197 KiB  
Review
Listeria monocytogenes: The Impact of Cell Death on Infection and Immunity
by Courtney E. McDougal and John-Demian Sauer
Pathogens 2018, 7(1), 8; https://doi.org/10.3390/pathogens7010008 - 11 Jan 2018
Cited by 24 | Viewed by 12444
Abstract
Listeria monocytogenes has evolved exquisite mechanisms for invading host cells and spreading from cell-to-cell to ensure maintenance of its intracellular lifecycle. As such, it is not surprising that loss of the intracellular replication niche through induction of host cell death has significant implications [...] Read more.
Listeria monocytogenes has evolved exquisite mechanisms for invading host cells and spreading from cell-to-cell to ensure maintenance of its intracellular lifecycle. As such, it is not surprising that loss of the intracellular replication niche through induction of host cell death has significant implications on the development of disease and the subsequent immune response. Although L. monocytogenes can activate multiple pathways of host cell death, including necrosis, apoptosis, and pyroptosis, like most intracellular pathogens L. monocytogenes has evolved a series of adaptations that minimize host cell death to promote its virulence. Understanding how L. monocytogenes modulates cell death during infection could lead to novel therapeutic approaches. In addition, as L. monocytogenes is currently being developed as a tumor immunotherapy platform, understanding how cell death pathways influence the priming and quality of cell-mediated immunity is critical. This review will focus on the mechanisms by which L. monocytogenes modulates cell death, as well as the implications of cell death on acute infection and the generation of adaptive immunity. Full article
(This article belongs to the Special Issue Listeria monocytogenes and Its Interactions with the Host)
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29 pages, 1808 KiB  
Review
Prion Strains and Transmission Barrier Phenomena
by Angélique Igel-Egalon, Vincent Béringue, Human Rezaei and Pierre Sibille
Pathogens 2018, 7(1), 5; https://doi.org/10.3390/pathogens7010005 - 1 Jan 2018
Cited by 28 | Viewed by 7494
Abstract
Several experimental evidences show that prions are non-conventional pathogens, which physical support consists only in proteins. This finding raised questions regarding the observed prion strain-to-strain variations and the species barrier that happened to be crossed with dramatic consequences on human health and veterinary [...] Read more.
Several experimental evidences show that prions are non-conventional pathogens, which physical support consists only in proteins. This finding raised questions regarding the observed prion strain-to-strain variations and the species barrier that happened to be crossed with dramatic consequences on human health and veterinary policies during the last 3 decades. This review presents a focus on a few advances in the field of prion structure and prion strains characterization: from the historical approaches that allowed the concept of prion strains to emerge, to the last results demonstrating that a prion strain may in fact be a combination of a few quasi species with subtle biophysical specificities. Then, we will focus on the current knowledge on the factors that impact species barrier strength and species barrier crossing. Finally, we present probable scenarios on how the interaction of strain properties with host characteristics may account for differential selection of new conformer variants and eventually species barrier crossing. Full article
(This article belongs to the Special Issue PrPSc prions: state of the art)
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