Mechanisms of community MRSA virulence

在2020财年，我们继续了我们在金黄色葡萄球菌发病机制方面的长期研究。我们研究的一个重要组成部分是利用动物感染模型来研究发病机制，和/或研究金黄色葡萄球菌与人中性粒细胞的相互作用。虽然大多数细菌很容易被中性粒细胞杀死，但一些金黄色葡萄球菌菌株已经进化出避开中性粒细胞破坏的机制，从而导致人类感染。值得注意的是，在包括美国在内的世界大部分地区，金黄色葡萄球菌是导致血液、皮肤和软组织以及下呼吸道感染的最常见原因之一。此外，在过去的几十年里，这种病原体对抗生素的耐药性越来越强，耐甲氧西林金黄色葡萄球菌(MRSA)是医疗保健相关感染的主要原因。因此，治疗选择是有限的。与医疗保健相关的耐甲氧西林金黄色葡萄球菌感染是具有易感风险因素的典型个人。相比之下，社区相关MRSA(CA-MRSA)会在其他健康的个人中引起疾病，这些感染可能是严重的或致命的。CA-MRSA出现在20世纪90年代，然后在接下来的十年里蔓延到世界各地。尽管最近医院MRSA感染人数有所下降，但CA-MRSA感染水平保持相对稳定。CA-MRSA菌株毒力增强和成功的分子基础尚未完全确定。

In FY2020, we continued our long-standing research in the area of Staphylococcus aureus pathogenesis. A significant component of our research utilizes animal infection models to study mechanisms of pathogenesis, and/or investigates interaction of S. aureus with human neutrophils. Although most bacteria are killed readily by neutrophils, some strains of S. aureus have evolved mechanisms to circumvent destruction by neutrophils and thereby cause human infections. Notably, Staphylococcus aureus is among the most frequent causes of bloodstream, skin and soft tissue, and lower respiratory tract infections in much of the world, including the United States. In addition, the pathogen has become increasingly resistant to antibiotics over the past several decades and methicillin-resistant S. aureus (MRSA) is a leading cause of healthcare-associated infections. Thus, treatment options are limited. Healthcare-associated MRSA infections are typical of individuals with predisposing risk factors. In contrast, community-associated MRSA (CA-MRSA) cause disease in otherwise healthy individuals, and these infections can be severe or fatal. CA-MRSA emerged in the 1990s and then spread worldwide over the next decade. Although there has been a recent decrease in the number of hospital MRSA infections, the level of CA-MRSA infections has remained relatively constant. The molecular basis for the increased virulence potential and success of CA-MRSA strains is incompletely defined.