Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA
Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA
复制标题
DOI：
10.1038/nm1656
复制
发表时间：
2007-12-01
期刊：
影响因子：
82.9
通讯作者：
Otto, Michael
中科院分区：
文献类型：
--
作者：
Wang, Rong;Braughton, Kevin R.;Otto, Michael
耐甲氧西林金黄色葡萄球菌（MRSA）仍然是一种主要的人类病原体。传统上，MRSA感染仅发生在医院，并仅限于免疫功能低下的患者或具有易感风险因素的个体。然而，最近社区相关（CA）-MRSA菌株引起了一场令人担忧的流行病，这可能导致严重感染，导致坏死性筋膜炎，甚至导致健康成人在医疗机构之外死亡（1，2）。在美国，CA-MRSA现在是导致急诊室旅行的大多数感染的原因（3）。目前还不清楚是什么使CA-MRSA菌株更成功地导致人类疾病相比，他们的医院相关的同行。在这里，我们描述了一类分泌的葡萄球菌肽，具有显著的能力，招募，激活和随后裂解人中性粒细胞，从而消除主要的细胞防御S。金黄色葡萄球菌感染。这些肽由标准CA-MRSA菌株以高浓度产生，并显著有助于菌株在动物感染模型中引起疾病的能力。我们的研究揭示了一个以前没有特征的S。金黄色葡萄球菌毒力因子，其至少部分地解释CA-MRSA的增强的毒力。
Methicillin-resistant Staphylococcus aureus (MRSA) remains a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings(1,2). In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room(3). It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. Here we describe a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study reveals a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA.