title: Contribution of CsrR-regulated virulence factors to the progress and outcome of murine skin infections by Streptococcus pyogenes.
abstract: Streptococcus pyogenes with null mutations in the csrRS regulatory locus are highly virulent in mice due to derepression of hyaluronic acid capsule synthesis and exotoxins, e.g., streptolysin S (SLS) and pyrogenic exotoxin B (SpeB). We generated derivatives of a DeltacsrRS strain that also carry deletions in hasAB (leading to an acapsular phenotype) or in sagA (phenotypically SLS-) or an interruption of speB (SpeB-) to test the relative contributions of these factors to the development of necrotic skin lesions. Inoculation of 2 x 10(6) to 4 x 10(6) CFU of either acapsular or SLS- strains into hairless mice resulted in lesions approximately 70% smaller than those of the DeltacsrRS parent strain. Elimination of SLS also reduced lethality from 100% to 0% at this inoculum (P < 10(-7); Fisher exact test). In contrast, SLS+ SpeB- mutants yielded lesions that were only 41% smaller than the parent strain (t = 2.2; P = 0.04), but only 3 the 17 lesions had dermal sloughing (P = 10(-5)). The nonulcerative lesions associated with SpeB- strains appeared pale with surrounding erythema. We conclude that capsule and SLS contribute to the subcutaneous spread of S. pyogenes and to a fatal outcome of infection. SpeB facilitates early dermal ulceration but has minor influence on lesion size and mortality. Large ulcerative lesions are observed only when both toxins are present.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0378, USA. cengleb@umich.edu
authors.forename: N Cary
authors.initials: NC
authors.lastname: Engleberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Heath
authors.forename: Kristal
authors.initials: K
authors.lastname: Vardaman
authors.forename: Victor J
authors.initials: VJ
authors.lastname: DiRita
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000502:physiology*; D006820:Hyaluronic Acid / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D012097:Repressor Proteins / Q000502:physiology*; D012874:Skin Diseases, Infectious / Q000209:etiology*; D013290:Streptococcal Infections / Q000209:etiology*; D013297:Streptococcus pyogenes / Q000472:pathogenicity*; D013301:Streptolysins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D012097:Repressor Proteins; D013301:Streptolysins; D037521:Virulence Factors; C026050:streptolysin S; D006820:Hyaluronic Acid; D003546:Cysteine Endopeptidases; C042477:streptopain