Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model.
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.
Kennedy
Adam D
AD
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Bubeck Wardenburg
Juliane
J
Gardner
Donald J
DJ
Long
Daniel
D
Whitney
Adeline R
AR
Braughton
Kevin R
KR
Schneewind
Olaf
O
DeLeo
Frank R
FR
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
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin