title: Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model.
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 (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.
authors: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
authors: Adam D
authors: AD
authors: Kennedy
authors: Juliane
authors: J
authors: Bubeck Wardenburg
authors: Donald J
authors: DJ
authors: Gardner
authors: Daniel
authors: D
authors: Long
authors: Adeline R
authors: AR
authors: Whitney
authors: Kevin R
authors: KR
authors: Braughton
authors: Olaf
authors: O
authors: Schneewind
authors: Frank R
authors: FR
authors: DeLeo
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006460:Hemolysin Proteins / Q000037:antagonists & inhibitors* / Q000172:deficiency; D006801:Humans; D007114:Immunization / Q000379:methods*; D007116:Immunization, Passive / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000473:pathology; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin