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Characterization of the effect of the histidine kinase CovS on response regulator phosphorylation in group A

Nicola Horstmann1, Pranoti Sahasrabhojane1, Miguel Saldaña1

  • 1Department of Infectious Diseases, MD Anderson Cancer Center, Houston, Texas, USA.

Infection and Immunity
|January 7, 2015
PubMed

Insights

Two-component systems (TCSs) regulate bacterial virulence. This study reveals how CovS influences CovR phosphorylation in Group A Streptococcus (GAS), impacting gene expression and explaining M1 GAS epidemiology.

Area of Science:

  • Bacterial genetics and molecular biology
  • Microbial pathogenesis
  • Gene regulation

Background:

  • Two-component gene regulatory systems (TCSs) are crucial for bacterial adaptation and infectivity.
  • The CovRS TCS is central to the virulence of Group A Streptococcus (GAS), a major human pathogen.

Purpose of the Study:

  • To characterize the impact of the CovS sensor kinase on CovR phosphorylation and GAS global gene expression.
  • To investigate the kinase and phosphatase activities of CovS and their influence on CovR phosphorylation status.
  • To understand the differences in CovRS function between GAS serotypes M1 and M3 and their epidemiological implications.

Main Methods:

  • Quantitative in vivo phosphorylation assays.
  • Construction and analysis of isoallelic GAS strains differing by single amino acid mutations in CovS.
  • Transcriptome analyses (RNA sequencing) to assess global gene expression changes.

Main Results:

  • CovS primarily phosphorylates CovR, repressing virulence factor genes.
  • Both kinase and phosphatase activities of CovS affect CovR phosphorylation.
  • Serotype M1 GAS strains exhibit higher phosphorylated CovR levels and distinct responses to environmental cues compared to serotype M3.
  • CovS inactivation in M1 GAS leads to greater changes in CovR phosphorylation and gene expression than in M3 GAS.

Conclusions:

  • CovS plays a dual role in regulating CovR phosphorylation, influencing GAS virulence.
  • Differences in CovS function between M1 and M3 GAS contribute to distinct epidemiological behaviors, including higher covS mutation rates in M1 strains during invasive infections.
  • This study links TCS molecular mechanisms to the epidemiology of severe bacterial infections.

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