| Abstrakt: |
ABSTRACTCertain Tn916insertions in the chromosome of an M1-type, nonmucoid Streptococcus pyogenesisolate (MGAS166) were previously shown to result in stable mucoidy with increased expression of the capsular synthetic genes. The transposon insertions in these strains are directly upstream of an apparent operon encoding a two-component regulatory system, designated csrR-csrS. Compared with MGAS166, these mucoid mutants are more hemolytic and cause significantly more tissue damage in a murine model of skin infection. To extend these observations, we constructed an in-frame deletion in the gene encoding the response regulator, csrR, and we evaluated the expression of other known S. pyogenesvirulence factors. We discovered that csrRmutants have enhanced transcription of sagA, a gene associated with streptolysin S (SLS) and speB, the gene encoding pyrogenic exotoxin B (SpeB). The mutants also express substantially higher SLS activity and SpeB antigen in late-exponential-phase cultures. There is no change in expression of emm, scpA,sic, or cpa(genes encoding other S. pyogenesvirulence factors). CsrR−strains but not the wild-type parental strain produce necrotizing lesions in a mouse model of subcutaneous infection. A double mutant with deletions in bothcsrRand the capsular synthesis genes caused fewer and smaller necrotic skin lesions than the csrRmutants. However, this nonmucoid csrRstrain was more likely than the wild type to yield necrotic lesions, suggesting that mucoidy contributes to virulence in this model of infection but that there are other csrR-regulated factors involved in the production of necrotic lesions. |
