Relevance of spontaneous fabT mutations to a streptococcal toxic shock syndrome to non-streptococcal toxic shock syndrome transition in the novel-type Streptococcus pyogenes isolates that lost a salRK.

Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Mutations in covR/S or rgg, negative regulators, can reportedly modulate the severity of infection in this pathogen. Recently, we showed that the regions encoding the SalR-SalK, a two-component regulatory system, were deleted in some emm 1-type isolates (named as novel-type'). In this study, the two novel STSS' isolates 10-85(stss) and 11-171(stss) were more virulent than the two novel non-STSS' isolates 11O-2(non) and 11T-3(non) when examined using a mouse model of invasive infection. Genome-sequencing experiments using the three strains 10-85(stss), 11-171(stss), and 11O-2(non) detected only one single nucleotide polymorphism that causes a non-synonymous mutation in fabT encoding a transcriptional regulator in strain 11O-2(non). Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non-STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O-2(non), suggesting that the mutation in fabT, but not in covR/S or rgg, is involved in the differential virulence among the novel-type clinical isolates. This type of non-synonymous fabT mutation was also identified in 12 non-STSS isolates (including 11O-2(non) and 11T-3(non)), and most of those 12 isolates showed impaired FabT function.