Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model

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

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

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 (Δhla) 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 Δhla 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.

Original languageEnglish
Pages (from-to)1050-1058
Number of pages9
JournalJournal of Infectious Diseases
Volume202
Issue number7
DOIs
StatePublished - Oct 1 2010

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