The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus
| Autor: | Sophie Brinster, Claire Poyart, Arnaud Firon, Asmaa Tazi, Shaynoor Dramsi, Patrick Trieu-Cuot, Philippe Glaser, Elisabeth Sauvage, Douglas T. Golenbock, Violette Da Cunha |
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| Přispěvatelé: | Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique des génomes - Genetics of Genomes (UMR 3525), Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), This work was supported by grants from the National Institute of Health (NIH R01 AI052455-06A1 to DTG and PTC), the Agence Nationale de la Recherche (ANR-10-BLAN-1321 FattyBact to CP and PTC, and Grant ANR-08-StrepRespire to CP), and by financial supports from the Pasteur Institute (to PTC), CNRS (to CP, PG, and PTC), INSERM and Université Paris Descartes (to CP). SB was the recipient of a postdoctoral fellowship from the Region Ile-de-France (DIM MalInf)., ANR-10-BLAN-1321,FattyBact,Impact des acides gras de l'hôte sur l'adaptation des pathogènes à Gram positif à bas pourcentage GC(2010), ANR-06-MIME-0035,StreRespire,Métabolisme respiratoire et capture de l'hème chez le streptocoque du groupe B: impact sur le commensalisme et la virulence.(2006), Lassailly-Bondaz, Anne, BLANC - Impact des acides gras de l'hôte sur l'adaptation des pathogènes à Gram positif à bas pourcentage GC - - FattyBact2010 - ANR-10-BLAN-1321 - BLANC - VALID, Programme Microbiologie, Immunologie et Maladies Emergentes - Métabolisme respiratoire et capture de l'hème chez le streptocoque du groupe B: impact sur le commensalisme et la virulence. - - StreRespire2006 - ANR-06-MIME-0035 - MIME - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP), Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Génétique des génomes, ANR-10-BLAN-1321, FattyBact, Impact des acides gras de l'hôte sur l'adaptation des pathogènes à Gram positif à bas pourcentage GC(2010), ANR-06-MIME-0035, StrepRespire, Métabolisme respiratoire et capture de l'hème chez le streptocoque du groupe B: impact sur le commensalisme et la virulence.(2006) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Histidine Kinase
Operon Gene Identification and Analysis MESH: Amino Acid Sequence Biochemistry MESH: Protein Structure Tertiary MESH: Streptococcal Infections Protein Interaction Mapping Phosphoprotein Phosphatases MESH: Epistasis Genetic MESH: Animals Biology (General) MESH: Bacterial Proteins Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Streptococci Genomics MESH: Hemolysis Functional Genomics Bacterial Pathogens 3. Good health Medicine Infectious diseases Group B streptococcal infection Virulence Factors QH301-705.5 Molecular Sequence Data Immunology MESH: Sequence Alignment Virulence Microbiology MESH: Protein-Serine-Threonine Kinases Molecular Genetics 03 medical and health sciences MESH: Gene Expression Profiling Bacterial Proteins Genetics Humans Amino Acid Sequence Biology Microbial Pathogens Molecular Biology MESH: Protein Kinases MESH: Virulence Factors MESH: Molecular Sequence Data MESH: Humans 030306 microbiology MESH: Protein Interaction Mapping Proteins Epistasis Genetic Pigments Biological MESH: Streptococcus agalactiae [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Regulatory Proteins Protein Structure Tertiary Transmembrane Proteins Mutation Parasitology Immunologic diseases. Allergy Protein Kinases MESH: Female MESH: Signal Transduction Genetic Screens MESH: Virulence MESH: Gene Expression Regulation Bacterial Female Signal transduction Research Article Signal Transduction MESH: Pigments Biological MESH: Mutation Protein family MESH: Rats Bacterial diseases Protein domain Protein Serine-Threonine Kinases Hemolysis Models Biological Streptococcus agalactiae Streptococcal Infections Virology MESH: Phosphoprotein Phosphatases Animals Gene Regulation Gene Networks Protein Interactions Gene 030304 developmental biology Gene Expression Profiling Histidine kinase MESH: Models Biological Gene Expression Regulation Bacterial RC581-607 Rats MESH: Oligonucleotide Array Sequence Analysis Gene Function [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Genome Expression Analysis Sequence Alignment |
| Zdroj: | PLoS Pathogens PLoS Pathogens, 2013, 9 (2), pp.e1003179. ⟨10.1371/journal.ppat.1003179⟩ PLoS Pathogens, Public Library of Science, 2013, 9 (2), pp.e1003179. ⟨10.1371/journal.ppat.1003179⟩ PLoS Pathogens, Vol 9, Iss 2, p e1003179 (2013) PLoS Pathogens, Public Library of Science, 2013, 9 (2), pp.e1003179. 〈10.1371/journal.ppat.1003179〉 |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1003179⟩ |
| Popis: | Group B Streptococcus (GBS), a common commensal of the female genital tract, is the leading cause of invasive infections in neonates. Expression of major GBS virulence factors, such as the hemolysin operon cyl, is regulated directly at the transcriptional level by the CovSR two-component system. Using a random genetic approach, we identified a multi-spanning transmembrane protein, Abx1, essential for the production of the GBS hemolysin. Despite its similarity to eukaryotic CaaX proteases, the Abx1 function is not involved in a post-translational modification of the GBS hemolysin. Instead, we demonstrate that Abx1 regulates transcription of several virulence genes, including those comprising the hemolysin operon, by a CovSR-dependent mechanism. By combining genetic analyses, transcriptome profiling, and site-directed mutagenesis, we showed that Abx1 is a regulator of the histidine kinase CovS. Overexpression of Abx1 is sufficient to activate virulence gene expression through CovS, overcoming the need for an additional signal. Conversely, the absence of Abx1 has the opposite effect on virulence gene expression consistent with CovS locked in a kinase-competent state. Using a bacterial two-hybrid system, direct interaction between Abx1 and CovS was mapped specifically to CovS domains involved in signal processing. We demonstrate that the CovSR two-component system is the core of a signaling pathway integrating the regulation of CovS by Abx1 in addition to the regulation of CovR by the serine/threonine kinase Stk1. In conclusion, our study reports a regulatory function for Abx1, a member of a large protein family with a characteristic Abi-domain, which forms a signaling complex with the histidine kinase CovS in GBS. Author Summary The gram-positive Streptococcus genus includes three major human pathogens that are members of the normal microflora: Streptococcus pneumoniae (also known as the pneumococcus), Streptococcus pyogenes (Group A Streptococcus), and Streptococcus agalactiae (Group B Streptococcus). Their carriage in the population is highly dynamic and mostly asymptomatic. However, each of these species can cause a wide spectrum of diseases, from local infections to systemic and fatal infections including septicemia and meningitis. Expression of streptococcal virulence-associated genes is tightly regulated at the transcriptional level. However, the signal(s) and the precise molecular events controlling the switch from commensalism to virulence are not yet understood. In this study, we identified and characterized a bacterial protein essential for virulence gene expression in Group B Streptococcus, the main pathogen of neonates. We show that this transmembrane protein, named Abx1, interacts with the histidine kinase CovS to modulate the activity of the major regulator of virulence CovR. We define how a core set of four proteins, Abx1, CovS, CovR, and the serine/threonine kinase Stk1, interact to control the expression of virulence genes in S. agalactiae. We propose that Abx1-like proteins, that are widespread in bacteria, might be part of a conserved mechanism of two-component system regulation. |
| Databáze: | OpenAIRE |
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