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The group A Streptococcus accessory protein RocA: regulatory activity, interacting partners and influence on disease potential.

Authors
  • Jain, Ira1
  • Danger, Jessica L1
  • Burgess, Cameron1
  • Uppal, Timsy1
  • Sumby, Paul1
  • 1 Department of Microbiology & Immunology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
Type
Published Article
Journal
Molecular Microbiology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jan 01, 2020
Volume
113
Issue
1
Pages
190–207
Identifiers
DOI: 10.1111/mmi.14410
PMID: 31660653
Source
Medline
Language
English
License
Unknown

Abstract

The group A Streptococcus (GAS) causes diseases that range from mild (e.g. pharyngitis) to severely invasive (e.g. necrotizing fasciitis). Strain- and serotype-specific differences influence the ability of isolates to cause individual diseases. At the center of this variability is the CovR/S two-component system and the accessory protein RocA. Through incompletely defined mechanisms, CovR/S and RocA repress the expression of more than a dozen immunomodulatory virulence factors. Alleviation of this repression is selected for during invasive infections, leading to the recovery of covR, covS or rocA mutant strains. Here, we investigated how RocA promotes CovR/S activity, identifying that RocA is a pseudokinase that interacts with CovS. Disruption of CovS kinase or phosphatase activities abolishes RocA function, consistent with RocA acting through the modulation of CovS activity. We also identified, in conflict with a previous study, that the RocA regulon includes the secreted protease-encoding gene speB. Finally, we discovered an inverse correlation between the virulence of wild-type, rocA mutant, covS mutant and covR mutant strains during invasive infection and their fitness in an ex vivo upper respiratory tract model. Our data inform on mechanisms that control GAS disease potential and provide an explanation for observed strain- and serotype-specific variability in RocA function. © 2019 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

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