Mechanisms of community MRSA virulence

在2015财年，我们调查了金黄色葡萄球菌等细菌病原体如何引起人类疾病。虽然大多数细菌很容易被pmn杀死，但一些金黄色葡萄球菌菌株已经进化出了规避中性粒细胞破坏的机制，从而引起人类感染。值得注意的是，在包括美国在内的世界许多地方，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，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。医疗保健相关的MRSA感染是具有易感危险因素的个体的典型。相比之下，社区相关性MRSA （CA-MRSA）在其他健康个体中引起疾病，这些感染可能是严重或致命的。CA-MRSA出现于20世纪90年代，然后在接下来的十年里传播到世界各地。虽然最近医院MRSA感染的数量有所下降，但CA-MRSA感染的水平保持相对稳定。CA-MRSA菌株增加的毒力潜力和成功的分子基础尚未完全确定。因此，该科的一个重要组成部分是针对这方面知识的不足。

In FY2015, we investigated how bacterial pathogens such as Staphylococcus aureus cause human disease. Although most bacteria are killed readily by PMNs, 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. Thus, a significant component of the Section is directed to address this deficiency in knowledge. Inasmuch as skin and soft tissue infections (SSTIs) are the most prominent manifestation of CA-MRSA infections, we used a rabbit skin infection model to investigate changes in the S. aureus transcriptome in vivo. Our findings provided additional insight into the pathogenesis of S. aureus SSTIs, including a temporal component of the host response (Malachowa et al., PLoS ONE, 2014). Other ongoing MRSA studies investigated the 1) interaction of S. aureus with components of the human immune system, 2) the ability of influenza A virus to alter the response of neutrophils to S. aureus, and 3) the transmission and succces of MRSA in correctional facilites (collaboration with Columbia University).