Association of CovRS Two-Component Regulatory System with NADase Induction by Clindamycin Treatment in Streptococcus pyogenes.

Administration of high-dose clindamycin (CLI) and penicillin is recommended for the treatment of streptococcal toxic shock syndrome (STSS). However, CLI-resistant strains have been identified worldwide. In this study, some CLI-resistant strains demonstrated increased extracellular activity of the NAD-glycohydrolase (NADase) exotoxin following CLI treatment. These results support our previous conclusion that CLI-susceptible and CLI-resistant Streptococcus pyogenes strains exhibit CLI-dependent NADase induction. Furthermore, we investigated the mechanism of this phenomenon using 13 types of two-component sensor knockout strains derived from the CLI-susceptible strain 1529 that has a CLI-dependent NADase induction phenotype. Among the knockout strains, only 1529ΔcovS lost the phenotype. Additionally, 1529ΔspeB, 1529Δmga, and 1529Δrgg retained the CLI-dependent NADase induction phenotype. These findings indicate that CovS is related to this phenotype in a SpeB-independent manner.