Targeting Staphylococcus aureus α-Toxin as a Novel Approach to Reduce Severity of Recurrent Skin and Soft-Tissue Infections
Targeting Staphylococcus aureus α-Toxin as a Novel Approach to Reduce Severity of Recurrent Skin and Soft-Tissue Infections
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DOI：
10.1093/infdis/jiu223
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发表时间：
2014-10-01
影响因子：
6.4
通讯作者：
Wardenburg, Juliane Bubeck
中科院分区：
文献类型：
--
作者：
Sampedro, Georgia R.;DeDent, Andrea C.;Wardenburg, Juliane Bubeck
金黄色葡萄球菌经常引起复发性皮肤和软组织感染（SSTI）。在儿科人群中，针对S.金黄色葡萄球菌α-毒素与复发性SSTI的发生率降低相关。使用复发性SSTI的新模型，我们证明了在原发感染期间a毒素的表达增加了复发性疾病的严重程度。在初次感染期间，显性阴性毒素突变体或毒素受体ADAM 10的小分子抑制剂对α毒素的拮抗作用降低了再感染脓肿的严重程度。在S.因此，金黄色葡萄球菌SSTI提供了一种新的治疗策略，以减轻原发性和复发性疾病。
Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus alpha-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of a-toxin during primary infection increases the severity of recurrent disease. Antagonism of alpha-toxin by either a dominant-negative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM10 during primary infection reduces reinfection abscess severity. Early neutralization of a-toxin activity during S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary and recurrent disease.