in the Negative Regulator, csrR, Responsible for the High Virulence of a Naturally Occurring Type M3 Group A Streptococcus Clinical Isolate

We previously reported that type M3 group A streptococcus (GAS) showed a wide range of 50 % lethal dose values in mice. Analysis using DNA arrays indicated that the most virulent strain, M3-f, expressed significantly higher levels of the products of several virulence genes than did the other M3 isolates. Sequencing of the csrS, csrR, luxS, and rgg genes in the isolates showed that the M-3f csrR gene contained a specific point mutation. Disruption of wild-type (wt) csrR in an M3 strain increased its virulence and the expression of hyaluronic acid, whereas complementation with wt but not type M3-f csrR attenuated these changes. Expression exper-iments showed that type M3-f CsrR counteracted the effects of wt CsrR. Although wt CsrR bound to the hasA promoter region, type M3-f CsrR did not. Thus, the high virulence of the type M3-f strain is associated with the decreased binding of type M3-f CsrR to its target sequences. Group A streptococcus (GAS) is responsible for a wide spectrum of human diseases, including streptococcal toxic shock syndrome (STSS). GAS can be subtyped according to the serotype or genotype of the M proteins expressed on the cell surface. Particular M types of GAS have been associated with certain diseases, which sug