Acidic stress enhances CovR/S-dependent gene repression through activation of the covR/S promoter in emm1-type group A Streptococcus

Chuan Chiang-Ni*, Huei Chuan Tseng, Chia Hui Hung, Cheng Hsun Chiu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

11 Scopus citations


Streptococcus pyogenes (group A Streptococcus) is a clinically important gram-positive bacterium that causes severe diseases with high mortality. Spontaneous mutations in genes encoding the CovR/CovS two-component regulatory system have been shown to derepress expression of virulence factors and are significantly associated with invasiveness of infections. Sensor kinase CovS senses environmental signals and then regulates the levels of phosphorylated CovR. In addition, CovS is responsible for survival of group A Streptococcus under acidic stress. How this system regulates the expression of CovR-controlled genes under acidic stress is not clear. This study shows that the expression of CovR-controlled genes, including hasA, ska, and slo, is repressed under acidic conditions by a CovS-dependent mechanism. Inactivation of CovS kinase activity or CovR protein phosphorylation derepresses the transcription of these genes under acidic conditions, suggesting that the phosphorylation of CovR is required for the repression of the CovR-controlled genes. Furthermore, the promoter activity of the covR/covS operon (pcov) was upregulated after 15 min of incubation under acidic conditions. Replacement of pcov with a constitutively activated promoter abrogated the acidic-stress-dependent repression of the genes, indicating that the pH-dependent pcov activity is directly involved in the repression of CovR-controlled genes. In summary, the present study shows that inactivation of CovS not only derepresses CovR-controlled genes but also abrogates the acidic-stress-dependent repression of the genes; these phenomena may significantly increase bacterial virulence during infection.

Original languageEnglish
Pages (from-to)329-339
Number of pages11
JournalInternational Journal of Medical Microbiology
Issue number6
StatePublished - 09 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier GmbH


  • Acidic stress
  • CovR/CovS
  • Group A Streptococcus
  • NADase
  • SLO


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