A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus

Autor: Susanne Holzmeister, Ulrike Resch, Philip Tinnefeld, Sergo Kasvandik, Emmanuelle Charpentier, Anaïs Le Rhun, Sun Nyunt Wai, Manfred Rohde, James A. Tsatsaronis, Gerald Stübiger
Přispěvatelé: Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Histidine Kinase
Streptococcus pyogenes
Virulence Factors
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology)
Molecular Biology
Microbiology
Biochemistry or Biopharmacy)
Biology
medicine.disease_cause
Microbiology
03 medical and health sciences
Bacterial Proteins
Virology
Extracellular
medicine
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi)
molekylärbiologi
mikrobiologi
biokemi eller biofarmaci)
Regulation of gene expression
Streptococcus
Vesicle
Secretory Vesicles
Histidine kinase
Intracellular Signaling Peptides and Proteins
High-Throughput Nucleotide Sequencing
Membrane Proteins
Gene Expression Regulation
Bacterial
biology.organism_classification
Lipids
Two-component regulatory system
QR1-502
Cell biology
Repressor Proteins
030104 developmental biology
Membrane
RNA
Bacteria
Research Article
Zdroj: mBio
mBio, Vol 7, Iss 6, p e00207-16 (2016)
mBio, Vol 7, Iss 6 (2016)
Popis: Export of macromolecules via extracellular membrane-derived vesicles (MVs) plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS), the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response.
IMPORTANCE Group A streptococcus (GAS) is a Gram-positive bacterial pathogen responsible for more than 500,000 deaths annually. Establishment of GAS infection is dependent on a suite of proteins exported via the general secretory pathway. Here, we show that GAS naturally produces extracellular vesicles with a unique lipid composition that are laden with proteins and RNAs. Interestingly, both virulence-associated proteins and RNA species were found to be differentially abundant in vesicles relative to the bacteria. Furthermore, we show that genetic disruption of the virulence-associated two-component regulator CovRS leads to an increase in vesicle production. This study comprehensively describes the protein, RNA, and lipid composition of GAS-secreted MVs and alludes to a regulatory system impacting this process.
Databáze: OpenAIRE
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