Mechanisms of community MRSA virulence

2012年，我实验室的一个主要研究重点是研究金黄色葡萄球菌等细菌病原体是如何引起人类疾病的。虽然大多数细菌很容易被pmn杀死，但某些金黄色葡萄球菌菌株已经进化出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大部分地区，金黄色葡萄球菌是引起血液感染、皮肤和软组织感染以及下呼吸道感染的最常见病原体。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）是医院获得性感染的主要原因。因此，治疗选择是有限的。医院获得性耐甲氧西林金黄色葡萄球菌感染也是具有易感危险因素的个体的典型感染。相反，社区相关（或获得性）MRSA （CA-MRSA）在其他健康个体中引起疾病，这些感染可能是严重/致命的。在世界范围内，CA-MRSA感染的数量相对较高，其中包括在美国持续流行的CA-MRSA感染。CA-MRSA发病率和严重程度增加的分子基础尚不清楚。我们假设细菌致病的能力很大程度上是由于病原体来源的因素改变了正常的中性粒细胞功能和个体宿主的易感性。因此，在细胞和分子水平上更好地了解细菌- pmn界面将为我们理解、治疗和控制由细菌病原体引起的疾病提供关键信息。金黄色葡萄球菌是检验我们假设的理想模型病原体，因为它是人类疾病的重要原因，它可能具有多重耐药性，因此难以根除，而中性粒细胞是抵抗金黄色葡萄球菌感染的第一道防线。迄今为止，我们的研究包括鉴定CA-MRSA用来逃避人类中性粒细胞破坏的基因和蛋白质，从而有助于毒力，生存和发病机制。

In 2012, a primary focus of research in my laboratory investigated how bacterial pathogens such as Staphylococcus aureus cause human disease. Although most bacteria are killed readily by PMNs, certain strains of S. aureus have evolved mechanisms to circumvent destruction by neutrophils and thereby cause human infections. Notably, S. aureus is the most frequent etiologic agent causing bloodstream infection, skin and soft tissue infection, and lower respiratory tract infection in much of the world, including the United States. In addition, the pathogen has become increasingly resistant to antibiotics over the past few decades and methicillin-resistant S. aureus (MRSA) is a leading cause of hospital-acquired infections. Thus, treatment options are limited. Hospital-acquired MRSA infections are also typical of individuals with predisposing risk factors. In contrast, community-associated (or acquired) MRSA (CA-MRSA) cause disease in otherwise healthy individuals, and these infections can be severe/fatal. There has been a relatively high number of CA-MRSA infections worldwide, and this includes an ongoing epidemic of CA-MRSA infections in the United States. The molecular basis for the increased incidence and severity of CA-MRSA disease is not known. We hypothesize that the ability of bacteria to cause disease is largely due to pathogen-derived factors that alter normal neutrophil function and individual host susceptibility. Therefore, a better understanding of the bacteria-PMN interface at the cell and molecular levels will provide information critical to our understanding, treatment, and control of disease caused by bacterial pathogens. S. aureus is an ideal model pathogen with which to test our hypothesis because it is an important cause of human disease, it can be multi-drug resistant and thus hard to eradicate, and neutrophils are the first line of defense against S. aureus infections. To date, our studies include identification of genes and proteins used by CA-MRSA to evade destruction by human neutrophils, hence contributing to virulence, survival and pathogenesis.