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

J Infect Dis. 2010 Oct 1;202(7):1050-8. doi: 10.1086/656043.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bacterial Toxins / antagonists & inhibitors*
  • Disease Models, Animal
  • Female
  • Gene Deletion
  • Hemolysin Proteins / antagonists & inhibitors*
  • Hemolysin Proteins / deficiency
  • Humans
  • Immunization / methods*
  • Immunization, Passive / methods*
  • Mice
  • Mice, Inbred BALB C
  • Skin / pathology
  • Staphylococcal Skin Infections / immunology*
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / pathogenicity


  • Bacterial Toxins
  • Hemolysin Proteins
  • staphylococcal alpha-toxin