Pathogens

45 pages, 2111 KB

Open AccessEditor’s ChoiceReview

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 70 | Viewed by 15460

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 KB

Open AccessEditor’s ChoiceArticle

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 26 | Viewed by 6531

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 KB

Open AccessFeature PaperEditor’s ChoiceReview

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 32 | Viewed by 7608

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 KB

Open AccessEditor’s ChoiceReview

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 7346

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 KB

Open AccessEditor’s ChoiceReview

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 96 | Viewed by 11048

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 KB

Open AccessFeature PaperEditor’s ChoiceReview

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 41 | Viewed by 7731

Abstract

Prion diseases are associated with the conversion of the cellular prion protein (PrP^C), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrP^Sc) that accumulates [...] Read more.

Prion diseases are associated with the conversion of the cellular prion protein (PrP^C), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrP^Sc) that accumulates in brain tissues of affected individuals. PrP^Sc is a self-catalytic protein assembly capable of recruiting native conformers of PrP^C, and causing their rearrangement into new PrP^Sc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrP^Sc, 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 PrP^Sc 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 PrP^C, 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 PrP^C 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 PrP^C, discussing pharmacological properties and therapeutic potentials of each chemical class. Full article

(This article belongs to the Special Issue PrP^Sc prions: state of the art)

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45 pages, 13782 KB

Open AccessFeature PaperEditor’s ChoiceReview

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 104 | Viewed by 15421

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 KB

Open AccessEditor’s ChoiceReview

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 53 | Viewed by 13317

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 KB

Open AccessFeature PaperEditor’s ChoiceOpinion

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 63 | Viewed by 8323

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 KB

Open AccessFeature PaperEditor’s ChoiceReview

The Structure of PrP^Sc Prions

by Holger Wille and Jesús R. Requena

Pathogens 2018, 7(1), 20; https://doi.org/10.3390/pathogens7010020 - 7 Feb 2018

Cited by 73 | Viewed by 23085

Abstract

PrP^Sc (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.

PrP^Sc (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. PrP^Sc is an alternatively folded variant of the cellular prion protein, PrP^C, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrP^C is well studied, the structure of PrP^Sc 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 PrP^Sc as a four-rung β-solenoid. A high-resolution structure of PrP^Sc 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 PrP^Sc. Here, we summarize the current knowledge regarding the structure of PrP^Sc and speculate about the molecular conversion mechanisms that leads from PrP^C to PrP^Sc. Full article

(This article belongs to the Special Issue PrP^Sc prions: state of the art)

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11 pages, 5359 KB

Open AccessEditor’s ChoiceReview

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 33 | Viewed by 9560

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 KB

Open AccessEditor’s ChoiceReview

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 36 | Viewed by 15481

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 KB

Open AccessEditor’s ChoiceReview

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 5348

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 KB

Open AccessEditor’s ChoiceReview

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 19 | Viewed by 7514

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 KB

Open AccessEditor’s ChoiceReview

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 13 | Viewed by 5051

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 KB

Open AccessEditor’s ChoiceReview

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 30 | Viewed by 14203

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 KB

Open AccessFeature PaperEditor’s ChoiceReview

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 32 | Viewed by 8779

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 PrP^Sc prions: state of the art)

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