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Special Issue "Microbial Virulence Factors"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 30 September 2019

Special Issue Editor

Guest Editor
Dr. Jorge H. Leitão

Bioengineering Department, Instituto Superior Técnico, Universidade de Lisboa. Av. Rovisco Pais, Torre Sul, Piso 6, 1049-001 Lisboa, Portugal
Website | E-Mail
Interests: bacterial pathogenesis; virulence factors; antimicrobials; bacterial exopolysaccharides; Gram-negative bacteria; molecular microbiology

Special Issue Information

Dear Colleagues,

Microbial virulence factors can be defined as a wide range of molecules produced by pathogenic microbes that enhance their ability to evade their host defenses and cause disease. This broad definition encompasses secreted products such as toxins, enzymes, exopolysaccharides, but also cell surface structures like capsules, lipopolysaccharides, glyco- and lipoproteins, and intracellular changes in metabolic regulatory networks governed by protein sensors/regulators and non-coding regulatory RNAs. The knowledge, at the molecular level, of the biology of microbial pathogens and their virulence factors is central in the development of novel therapeutic molecules and strategies to combat microbial infections. This is of particular importance in the present days with the worldwide emergence of microbes resistant to available antimicrobials. Advances in recent years in molecular biology, genomic technologies and bioinformatics contributed to the molecular identification and functional analyses of microbial virulence factors. This Special Issue of IJMS will be focused on virulence factors and their regulatory networks from microbes such as bacteria, viruses, fungi, and parasites, as well as on the description of innovative experimental techniques to characterize microbial virulence factors. Research papers, up-to-date review articles, and commentaries are all welcome.

Prof. Jorge H. Leitão
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pathogenic bacteria
  • toxins
  • bacterial capsules
  • fungal virulence factors
  • virus virulence factors
  • host defense evasion
  • intracellular survival
  • virulence determinants
  • human microbial parasites

Published Papers (7 papers)

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Research

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Open AccessArticle
Relation of the pdxB-usg-truA-dedA Operon and the truA Gene to the Intracellular Survival of Salmonella enterica Serovar Typhimurium
Int. J. Mol. Sci. 2019, 20(2), 380; https://doi.org/10.3390/ijms20020380
Received: 17 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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Abstract
Salmonella is the genus of Gram-negative, facultative intracellular pathogens that have the ability to infect large numbers of animal or human hosts. The S. enterica usg gene is associated with intracellular survival based on ortholog screening and identification. In this study, the λ-Red [...] Read more.
Salmonella is the genus of Gram-negative, facultative intracellular pathogens that have the ability to infect large numbers of animal or human hosts. The S. enterica usg gene is associated with intracellular survival based on ortholog screening and identification. In this study, the λ-Red recombination system was used to construct gene deletion strains and to investigate whether the identified operon was related to intracellular survival. The pdxB-usg-truA-dedA operon enhanced the intracellular survival of S. enterica by resisting the oxidative environment and the usg and truA gene expression was induced by H2O2. Moreover, the genes in this operon (except for dedA) contributed to virulence in mice. These findings indicate that the pdxB-usg-truA-dedA operon functions in resistance to oxidative environments during intracellular survival and is required for in vivo S. enterica virulence. This study provides insight toward a better understand of the characteristics of intracellular pathogens and explores the gene modules involved in their intracellular survival. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
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Open AccessArticle
Proteomics Analysis of SsNsd1-Mediated Compound Appressoria Formation in Sclerotinia sclerotiorum
Int. J. Mol. Sci. 2018, 19(10), 2946; https://doi.org/10.3390/ijms19102946
Received: 10 September 2018 / Revised: 21 September 2018 / Accepted: 24 September 2018 / Published: 27 September 2018
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Abstract
Sclerotinia sclerotiorum (Lib.) de Bary is a devastating necrotrophic fungal pathogen attacking a broad range of agricultural crops. In this study, although the transcript accumulation of SsNsd1, a GATA-type IVb transcription factor, was much lower during the vegetative hyphae stage, its mutants completely [...] Read more.
Sclerotinia sclerotiorum (Lib.) de Bary is a devastating necrotrophic fungal pathogen attacking a broad range of agricultural crops. In this study, although the transcript accumulation of SsNsd1, a GATA-type IVb transcription factor, was much lower during the vegetative hyphae stage, its mutants completely abolished the development of compound appressoria. To further elucidate how SsNsd1 influenced the appressorium formation, we conducted proteomics-based analysis of the wild-type and ΔSsNsd1 mutant by two-dimensional electrophoresis (2-DE). A total number of 43 differentially expressed proteins (≥3-fold change) were observed. Of them, 77% were downregulated, whereas 14% were upregulated. Four protein spots fully disappeared in the mutants. Further, we evaluated these protein sequences by mass spectrometry analysis of the peptide mass and obtained functionally annotated 40 proteins, among which only 17 proteins (38%) were identified to have known functions including energy production, metabolism, protein fate, stress response, cellular organization, and cell growth and division. However, the remaining 23 proteins (56%) were characterized as hypothetical proteins among which four proteins (17%) were predicted to contain the signal peptides. In conclusion, the differentially expressed proteins identified in this study shed light on the ΔSsNsd1 mutant-mediated appressorium deficiency and can be used in future investigations to better understand the signaling mechanisms of SsNsd1 in S. sclerotiorum. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
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Open AccessArticle
Discovery of lahS as a Global Regulator of Environmental Adaptation and Virulence in Aeromonas hydrophila
Int. J. Mol. Sci. 2018, 19(9), 2709; https://doi.org/10.3390/ijms19092709
Received: 18 August 2018 / Revised: 3 September 2018 / Accepted: 4 September 2018 / Published: 11 September 2018
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Abstract
Aeromonas hydrophila is an important aquatic microorganism that can cause fish hemorrhagic septicemia. In this study, we identified a novel LysR family transcriptional regulator (LahS) in the A. hydrophila Chinese epidemic strain NJ-35 from a library of 947 mutant strains. The deletion of [...] Read more.
Aeromonas hydrophila is an important aquatic microorganism that can cause fish hemorrhagic septicemia. In this study, we identified a novel LysR family transcriptional regulator (LahS) in the A. hydrophila Chinese epidemic strain NJ-35 from a library of 947 mutant strains. The deletion of lahS caused bacteria to exhibit significantly decreased hemolytic activity, motility, biofilm formation, protease production, and anti-bacterial competition ability when compared to the wild-type strain. In addition, the determination of the fifty percent lethal dose (LD50) in zebrafish demonstrated that the lahS deletion mutant (ΔlahS) was highly attenuated in virulence, with an approximately 200-fold increase in LD50 observed as compared with that of the wild-type strain. However, the ΔlahS strain exhibited significantly increased antioxidant activity (six-fold). Label-free quantitative proteome analysis resulted in the identification of 34 differentially expressed proteins in the ΔlahS strain. The differentially expressed proteins were involved in flagellum assembly, metabolism, redox reactions, and cell density induction. The data indicated that LahS might act as a global regulator to directly or indirectly regulate various biological processes in A. hydrophila NJ-35, contributing to a greater understanding the pathogenic mechanisms of A. hydrophila. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
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Review

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Open AccessReview
Divergent Approaches to Virulence in C. albicans and C. glabrata: Two Sides of the Same Coin
Int. J. Mol. Sci. 2019, 20(9), 2345; https://doi.org/10.3390/ijms20092345
Received: 10 April 2019 / Revised: 8 May 2019 / Accepted: 8 May 2019 / Published: 11 May 2019
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Abstract
Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful [...] Read more.
Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful in causing human candidiasis. In this review, the virulence mechanisms employed by C. albicans and C. glabrata are analyzed, with emphasis on the differences between the two systems. Pathogenesis features considered in this paper include dimorphic growth, secreted enzymes and signaling molecules, and stress resistance mechanisms. The consequences of these traits in tissue invasion, biofilm formation, immune system evasion, and macrophage escape, in a species dependent manner, are discussed. This review highlights the observation that C. albicans and C. glabrata follow different paths leading to a similar outcome. It also highlights the lack of knowledge on some of the specific mechanisms underlying C. glabrata pathogenesis, which deserve future scrutiny. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
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Open AccessReview
Catching a SPY: Using the SpyCatcher-SpyTag and Related Systems for Labeling and Localizing Bacterial Proteins
Int. J. Mol. Sci. 2019, 20(9), 2129; https://doi.org/10.3390/ijms20092129
Received: 2 April 2019 / Revised: 25 April 2019 / Accepted: 26 April 2019 / Published: 30 April 2019
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Abstract
The SpyCatcher-SpyTag system was developed seven years ago as a method for protein ligation. It is based on a modified domain from a Streptococcus pyogenes surface protein (SpyCatcher), which recognizes a cognate 13-amino-acid peptide (SpyTag). Upon recognition, the two form a covalent isopeptide [...] Read more.
The SpyCatcher-SpyTag system was developed seven years ago as a method for protein ligation. It is based on a modified domain from a Streptococcus pyogenes surface protein (SpyCatcher), which recognizes a cognate 13-amino-acid peptide (SpyTag). Upon recognition, the two form a covalent isopeptide bond between the side chains of a lysine in SpyCatcher and an aspartate in SpyTag. This technology has been used, among other applications, to create covalently stabilized multi-protein complexes, for modular vaccine production, and to label proteins (e.g., for microscopy). The SpyTag system is versatile as the tag is a short, unfolded peptide that can be genetically fused to exposed positions in target proteins; similarly, SpyCatcher can be fused to reporter proteins such as GFP, and to epitope or purification tags. Additionally, an orthogonal system called SnoopTag-SnoopCatcher has been developed from an S. pneumoniae pilin that can be combined with SpyCatcher-SpyTag to produce protein fusions with multiple components. Furthermore, tripartite applications have been produced from both systems allowing the fusion of two peptides by a separate, catalytically active protein unit, SpyLigase or SnoopLigase. Here, we review the current state of the SpyCatcher-SpyTag and related technologies, with a particular emphasis on their use in vaccine development and in determining outer membrane protein localization and topology of surface proteins in bacteria. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
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Open AccessReview
Coagulase-Negative Staphylococci Pathogenomics
Int. J. Mol. Sci. 2019, 20(5), 1215; https://doi.org/10.3390/ijms20051215
Received: 22 January 2019 / Revised: 28 February 2019 / Accepted: 7 March 2019 / Published: 11 March 2019
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Abstract
Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus [...] Read more.
Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus pathogenicity. In the last decade, numerous CoNS whole-genome sequences have been released, leading to the identification of numerous putative virulence factors. Koch’s postulates and the molecular rendition of these postulates, established by Stanley Falkow in 1988, do not explain the microbial pathogenicity of CoNS. However, whole-genome sequence data has shed new light on CoNS pathogenicity. In this review, we analyzed the contribution of genomics in defining CoNS virulence, focusing on the most frequent and pathogenic CoNS species: S. epidermidis, S. haemolyticus, S. saprophyticus, S. capitis, and S. lugdunensis. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
Open AccessReview
Small Noncoding Regulatory RNAs from Pseudomonas aeruginosa and Burkholderia cepacia Complex
Int. J. Mol. Sci. 2018, 19(12), 3759; https://doi.org/10.3390/ijms19123759
Received: 31 October 2018 / Revised: 22 November 2018 / Accepted: 23 November 2018 / Published: 27 November 2018
PDF Full-text (613 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cystic fibrosis (CF) is the most life-limiting autosomal recessive disorder in Caucasians. CF is characterized by abnormal viscous secretions that impair the function of several tissues, with chronic bacterial airway infections representing the major cause of early decease of these patients. Pseudomonas aeruginosa [...] Read more.
Cystic fibrosis (CF) is the most life-limiting autosomal recessive disorder in Caucasians. CF is characterized by abnormal viscous secretions that impair the function of several tissues, with chronic bacterial airway infections representing the major cause of early decease of these patients. Pseudomonas aeruginosa and bacteria from the Burkholderia cepacia complex (Bcc) are the leading pathogens of CF patients’ airways. A wide array of virulence factors is responsible for the success of infections caused by these bacteria, which have tightly regulated responses to the host environment. Small noncoding RNAs (sRNAs) are major regulatory molecules in these bacteria. Several approaches have been developed to study P. aeruginosa sRNAs, many of which were characterized as being involved in the virulence. On the other hand, the knowledge on Bcc sRNAs remains far behind. The purpose of this review is to update the knowledge on characterized sRNAs involved in P. aeruginosa virulence, as well as to compile data so far achieved on sRNAs from the Bcc and their possible roles on bacteria virulence. Full article
(This article belongs to the Special Issue Microbial Virulence Factors)
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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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