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.