Identification of novel substrates of Shigella T3SA through analysis of its virulence plasmid-encoded secretome
| Autor: | Laurie Pinaud, Philippe J. Sansonetti, Mariana L. Ferrari, Armelle Phalipon, Robin C. Friedman, Martin von Bergen, François-Xavier Campbell-Valois, Nico Jehmlich |
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| Přispěvatelé: | Pathogénie microbienne moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Biologie systémique - Systems Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Universität Leipzig [Leipzig], Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), University of Ottawa [Ottawa], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig, Collège de France - Chaire Microbiologie et Maladies infectieuses |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Bacterial Diseases Proteome MESH: Shigella flexneri Physiology lcsh:Medicine MESH: beta-Lactamases MESH: Virulence medicine.disease_cause Pathology and Laboratory Medicine Toxicology Biochemistry Mass Spectrometry Shigella flexneri Jurkat Cells Plasmid Medicine and Health Sciences MESH: Jurkat Cells Shigella lcsh:Science Yersinia enterocolitica MESH: Bacterial Proteins Multidisciplinary biology Bacterial Gastroenteritis Virulence Effector 3. Good health Bacterial Pathogens Gastroenteritis MESH: Proteome Protein Transport Infectious Diseases Salmonella enterica Medical Microbiology Cell Processes Shigellosis Pathogens Research Article Neglected Tropical Diseases Plasmids 030106 microbiology Immunoblotting Molecular Probe Techniques Gastroenterology and Hepatology Research and Analysis Methods Microbiology beta-Lactamases 03 medical and health sciences Bacterial Proteins MESH: Plasmids Virology medicine Humans Secretion Molecular Biology Techniques Microbial Pathogens Molecular Biology MESH: Mass Spectrometry MESH: Humans Bacteria lcsh:R Host Cells Organisms Biology and Life Sciences Protein Secretion Proteins Cell Biology biology.organism_classification Tropical Diseases [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology 030104 developmental biology MESH: HeLa Cells lcsh:Q Antitoxins Physiological Processes Viral Transmission and Infection HeLa Cells |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2017, 12 (10), pp.e0186920. ⟨10.1371/journal.pone.0186920⟩ PLoS ONE, 2017, 12 (10), pp.e0186920. ⟨10.1371/journal.pone.0186920⟩ PLoS ONE, Vol 12, Iss 10, p e0186920 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0186920⟩ |
| Popis: | International audience; Many human Gram-negative bacterial pathogens express a Type Three Secretion Apparatus (T3SA), including among the most notorious Shigella spp., Salmonella enterica, Yersinia enterocolitica and enteropathogenic Escherichia coli (EPEC). These bacteria express on their surface multiple copies of the T3SA that mediate the delivery into host cells of specific protein substrates critical to pathogenesis. Shigella spp. are Gram-negative bacterial pathogens responsible for human bacillary dysentery. The effector function of several Shigella T3SA substrates has largely been studied but their potential cellular targets are far from having been comprehensively delineated. In addition, it is likely that some T3SA substrates have escaped scrutiny as yet. Indeed, sequencing of the virulence plasmid of Shigella flexneri has revealed numerous open reading frames with unknown functions that could encode additional T3SA substrates. Taking advantage of label-free mass spectrometry detection of proteins secreted by a constitutively secreting strain of S. flexneri, we identified five novel substrates of the T3SA. We further confirmed their secretion through the T3SA and translocation into host cells using β-lactamase assays. The coding sequences of two of these novel T3SA substrates (Orf13 and Orf131a) have a guanine-cytosine content comparable to those of T3SA components and effectors. The three other T3SA substrates identified (Orf48, Orf86 and Orf176) have significant homology with antitoxin moieties of type II Toxin-Antitoxin systems usually implicated in the maintenance of low copy plasmids. While Orf13 and Orf131a might constitute new virulence effectors contributing to S. flexneri pathogenicity, potential roles for the translocation into host cells of antitoxins or antitoxin-like proteins during Shigella infection are discussed. |
| Databáze: | OpenAIRE |
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