CovS modulates the antimicrobial susceptibility of Streptococcus pyogenes

In Streptococcus pyogenes , the relationship between the major virulent regulatory factors, CovR/S, Mga, and Rgg, and antimicrobial susceptibility has not been elucidated till date. This study aimed to determine whether the inactivation of each regulatory factor affects antimicrobial susceptibility. We used covS , mga , and rgg knockout mutants from 3 different emm1 Streptococcus pyogenes strains with respect to the CovS amino acid sequence and investigated their susceptibility pattern to 29 antibiotics. Further, we investigated antimicrobial susceptibility of other 8 emm1 clinical isolates. The antibiotic susceptibility, particularly the susceptibility to penicillins, of the covS mutant strains was greater than that of the wild-type strains and the mga and rgg mutants. The covS complemented strain almost restored the susceptibility. The susceptibility to beta lactam in 1 strain with 2 amino acid sequence differences in CovS was higher than that of the other 2 strains with none or 1 amino acid sequence difference. Eight clinical isolates were classified into 2 groups based on antimicrobial susceptibility which correlate CovS amino acid sequence. The two-component signal transduction sensor protein CovS affects the susceptibility to antibiotics in Streptococcus pyogenes via the amino acid difference of CovS sequence.