Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027121 (
myositis
)
4,538
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Streptococcus pyogenes secretes many toxins that facilitate human colonization, invasion, and dissemination. NADase (
SPN
) and streptolysin O (SLO) are two toxins that play important roles in pathogenesis. We previously showed that increased production of
SPN
and SLO in epidemic serotype M1 and M89 S. pyogenes strains is associated with rapid intercontinental spread and enhanced virulence. The biological functions of
SPN
and SLO have been extensively studied using eukaryotic cell lines, but the relative contribution of each of these two toxins to pathogenesis of epidemic M1 or M89 strains remains unexplored. Herein, using a genetically representative epidemic M1 strain and a panel of isogenic mutant derivative strains, we evaluated the relative contributions of
SPN
and SLO toxins to virulence in mouse models of necrotizing
myositis
, bacteremia, and skin and soft tissue infection. We found that isogenic mutants lacking
SPN
, SLO, and both toxins are equally impaired in ability to cause necrotizing
myositis
. In addition, mutants lacking either
SPN
or SLO are significantly attenuated in the bacteremia and soft tissue infection models, and the mutant strain lacking production of both toxins is further attenuated. The mutant strain lacking both
SPN
and SLO production is severely attenuated in ability to resist killing by human polymorphonuclear leukocytes. We conclude that both
SPN
and SLO contribute significantly to S. pyogenes pathogenesis in these virulence assays.
...
PMID:Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections. 2803 2