Role of Rgg in the Pathogenesis of Invasive Covr/Covs Mutants of Group a Streptococcus

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

In the past decade, the outbreaks of invasive and non-invasive (scarlet fever) group A Streptococcus (GAS) infections were reported frequently worldwide. Results from the next generation sequencing revealed that bacterial isolates with spontaneous mutations in the covR/covS genes are closely related to the increase of bacterial virulence and severe clinical manifestations. CovR/CovS is a two-component regulatory system; the membrane-embedded CovS senses environmental signals and phosphorylates intracellular CovR protein upon activation. The phosphorylated CovR majorly acts as a transcriptional repressor; therefore, mutations in the covS gene results in the derepression of virulence factors expression and the increase of bacterial invasiveness. Mutations in the quorum-sensing regulatory factor rgg gene are also related to invasive GAS infections. The transcription of rgg is repressed in the covS mutant, which is consistent with the observations from clinical isolates. Nonetheless, although the covR mutant is more virulent than the wild-type strain, the transcription of rgg is upregulated in the covR mutant. The regulatory activity of Rgg has been shown to be inhibited by the endopeptidase PepO. The transcription of pepO is negatively regulated by the CovR/CovS; therefore, although the transcription of rgg is upregulated in the covR mutant, the regulatory activity of Rgg would be downregulated by the increased level of pepO. Importantly, this repression may contribute significantly to the increase of bacterial virulence. Based on these observations, how the repression of Rgg transcription and/or regulatory activity contributes to the pathogenesis of invasive covR/covS mutants will be elucidated. In addition, whether the regulatory activity of Rgg could be served as a marker for screening invasive GAS strains will also be evaluated. Invasive GAS infection is a disease with quick progress and high mortality. Results from this proposal will reveal the undefined roles of Rgg in invasive GAS infection and would be helpful for developing novel strategies for preventing invasive GAS infections.

Project IDs

Project ID:PC10907-0885
External Project ID:MOST109-2320-B182-036
StatusFinished
Effective start/end date01/08/2031/07/21

Keywords

  • Streptococcus
  • Two-component regulatory system
  • Bacterial pathogenesis
  • Bacterial gene regulation

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