Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
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.
社区相关性耐甲氧西林金黄色葡萄球菌（CA-MRSA）感染主要影响皮肤和软组织。尽管已经取得了一些进展，但我们对导致 CA-MRSA 皮肤感染发病机制的分子的了解还不完全。我们检验了假说，即α-溶血素（Hla）有助于 USA300 皮肤感染在小鼠中的严重程度，并确定针对 Hla 的疫苗接种是否会降低疾病严重程度。同源性 hla 阴性（Deltahla）株在小鼠感染模型中引起的皮肤损伤明显小于野生型 USA300 和 Newman 株引起的皮肤损伤。此外，野生型菌株引起的感染导致皮肤坏死性皮肤损伤，而感染 Deltahla 株的小鼠几乎没有或没有皮肤坏死。用 Hla 特异性抗血清进行被动免疫或用非毒性形式的 Hla 进行主动免疫可显著减少 USA300 引起的皮肤损伤的大小，并防止皮肤坏死。我们得出结论，Hla 是治疗或疫苗设计用于减轻严重金黄色葡萄球菌皮肤感染的潜在目标。
