A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B

• Published in: Infection and immunity Vol. 67; no. 10; pp. 5298 - 5305
• Main Authors: HEATH, A, DIRITA, V. J, BARG, N. L, ENGLEBERG, N. C
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.10.1999
• Subjects: Animals; Bacterial Capsules - metabolism; Bacterial Proteins; Bacteriology; Biological and medical sciences; Cysteine Endopeptidases - biosynthesis; Fundamental and applied biological sciences. Psychology; Hyaluronic Acid - biosynthesis; Male; Mice; Microbiology; Molecular and Cellular Pathogenesis; Mutation; Operon; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Skin Diseases, Infectious - etiology; Soft Tissue Infections - etiology; Streptococcus pyogenes; Streptococcus pyogenes - genetics; Streptococcus pyogenes - pathogenicity; Streptolysins - biosynthesis; Virulence; Virulence; Host agent relation; Repression; Gene expression; Microorganism capsule; Pathogenicity; Streptococcaceae; Regulation(control); Bacteria; Glycosaminoglycan; Micrococcales; Streptococcus pyogenes; Hyaluronic acid
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.67.10.5298-5305.1999

Certain Tn916 insertions in the chromosome of an M1-type, nonmucoid Streptococcus pyogenes isolate (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. pyogenes virulence factors. We discovered that csrR mutants 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. pyogenes virulence 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 both csrR and the capsular synthesis genes caused fewer and smaller necrotic skin lesions than the csrR mutants. However, this nonmucoid csrR strain 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.