Mechanisms of community MRSA virulence

在2015财政年度，我们调查了金黄色葡萄球菌等细菌病原体如何导致人类疾病。尽管大多数细菌很容易被中性粒细胞杀死，但一些S.金黄色葡萄球菌已经进化出机制来避免嗜中性粒细胞的破坏，从而引起人类感染。值得注意的是，金黄色葡萄球菌是包括美国在内的世界大部分地区血液、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，该病原体对抗生素的耐药性越来越强，耐甲氧西林的S。金黄色葡萄球菌（MRSA）是医疗保健相关感染的主要原因。因此，治疗选择有限。医疗保健相关的MRSA感染是具有易感风险因素的典型个体。相比之下，社区相关MRSA（CA-MRSA）在其他健康个体中引起疾病，这些感染可能是严重的或致命的。CA-MRSA出现于20世纪90年代，然后在接下来的十年中在全球范围内传播。虽然最近医院MRSA感染的数量有所减少，但CA-MRSA感染的水平保持相对稳定。CA-MRSA菌株的毒力潜力增加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解决这一知识不足的问题。 由于皮肤和软组织感染（SSTI）是CA-MRSA感染最突出的表现，我们使用兔皮肤感染模型来研究S。金黄色葡萄球菌体内转录组。我们的研究结果为S.金黄色葡萄球菌SSTI，包括宿主应答的时间成分（Malachowa等，PLoS ONE，2014）。 其他正在进行的MRSA研究调查了1）S。金黄色葡萄球菌与人类免疫系统的组分，2）甲型流感病毒改变中性粒细胞对金黄色葡萄球菌的反应的能力。金黄色葡萄球菌，和3）MRSA在教养设施中的传播和成功（与哥伦比亚大学合作）。

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).