Effect of phosphatase activity of the control of virulence sensor (CoVS) on clindamycin-mediated streptolysin O production in group A Streptococcus

Chuan Chiang-Ni*, Huei Chuan Tseng, Yong An Shi, Cheng Hsun Chiu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations

Abstract

Severe manifestations of group A Streptococcus (GAS) infections are associated with massive tissue destruction and high mortality. Clindamycin (CLI), a bacterial protein synthesis inhibitor, is recommended for treating patients with severe invasive GAS infection. Nonetheless, the subinhibitory concentration of CLI induces the production of GAS virulent exoproteins, such as streptolysin O (SLO) and NADase, which would enhance bacterial virulence and invasiveness. A better understanding of the molecular mechanism of how CLI triggers GAS virulence factor expression will be critical to develop appropriate therapeutic approaches. The present study shows that CLI activates SLO and NADase expressions in the emm1-type CLI-susceptible wild-type strain but not in covS or control of virulence sensor (CovS) phosphatase-inactivated mutants. Supplementation with Mg2+, which is a CovS phosphatase inhibitor, inhibits the CLI-mediated SLO upregulation in a dose-dependent manner in CLI-susceptible and CLI-resistant strains. These results not only reveal that the phosphorylation of response regulator CovR is essential for responding to CLI stimuli, but also suggest that inhibiting the phosphatase activity of CovS could be a potential strategy for the treatment of invasive GAS infection with CLI.

Original languageEnglish
Article numbere00583-19
JournalInfection and Immunity
Volume87
Issue number12
DOIs
StatePublished - 01 12 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords

  • Clindamycin
  • CovR/CovS
  • Group A Streptococcus
  • NADase
  • SLO

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