Association of CovRS two-component regulatory system with NADase induction by Clindamycin treatment in Streptococcus pyogenes.

The administration of high-dose clindamycin (CLI) along with penicillin is recommended for the treatment of streptococcal toxic shock syndrome (STSS). However, CLI-resistant strains have been identified worldwide. Firstly, in this study, some CLI-resistant strains showed increased extracellular activities of the NAD- glycohydrolase (NADase) exotoxin after CLI treatment. This result supported our previous conclusion that not only CLI-susceptible but also CLI-resistant S. pyogenes strains show the CLI-dependent NADase induction. Secondary, using the 13 types of two- component-sensor knockout strains derived from a CLI-susceptible strain 1529 that has the CLI-dependent NADase induction phenotype, we investigated the mechanism of action. Among the knockout strains, only 1529ΔcovS lost the phenotype. In addition, 1529ΔspeB, 1529Δmga, and 1529Δrgg retained the CLI-dependent NADase induction phenotype. These results suggest that CovS is related to the phenotype in SpeB independent manner.