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Targeting of Alpha‐Hemolysin by Active or Passive Immunization Decreases Severity of USA300 Skin Infection in a Mouse Model

2010; Oxford University Press; Volume: 202; Issue: 7 Linguagem: Inglês

10.1086/656043

1537-6613

Adam D. Kennedy, Juliane Bubeck Wardenburg, Donald J. Gardner, Daniel D. Long, Adeline R. Whitney, Kevin R. Braughton, Olaf Schneewind, Frank R. DeLeo,

Antimicrobial Peptides and Activities

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are predominantly those affecting skin and soft tissues. Although progress has been made, our knowledge of the molecules that contribute to the pathogenesis of CA-MRSA skin infections is incomplete. We tested the hypothesis that alpha-hemolysin (Hla) contributes to the severity of USA300 skin infections in mice and determined whether vaccination against Hla reduces disease severity. Isogenic hla-negative (Deltahla) strains caused skin lesions in a mouse infection model that were significantly smaller than those caused by wild-type USA300 and Newman strains. Moreover, infection due to wild-type strains produced dermonecrotic skin lesions, whereas there was little or no dermonecrosis in mice infected with Deltahla strains. Passive immunization with Hla-specific antisera or active immunization with a nontoxigenic form of Hla significantly reduced the size of skin lesions caused by USA300 and prevented dermonecrosis. We conclude that Hla is a potential target for therapeutics or vaccines designed to moderate severe S. aureus skin infections.