Mechanisms of staphylococcal skin colonization

摘要 这个多PI项目的目标是了解葡萄球菌是如何。绑定到皮肤表面。虽然S。 金黄色葡萄球菌能够引起人类的重大疾病，大多数是葡萄球菌。不要引起 疾病，而是作为共生体或互助者，附着在皮肤表面，提供有益的方面 敬东道主。这些好处包括通过合成独特的抗菌剂来抑制病原体定植。 除了适当的免疫系统发育外，还有化合物。然而，我们不知道如何 葡萄球菌会附着在皮肤上。这一应用假设，定居的葡萄球菌物种 人类通过结合角膜细胞的AAP(或金黄色葡萄球菌中的SasG)同源基因以一种保守的方式做到这一点。AAP 是一种棒状纤维蛋白，它在最初与角膜细胞的黏附中起作用，但也起到中介作用 细胞间堆积。为了解决这一假设，我们提出了以下具体目标：(1) 了解AAP介导的角膜细胞黏附的动力学；(2)确定AAP的配基特异性和 SasG凝集素结构域和(3)研究金黄色葡萄球菌SasG依赖的皮肤定植机制。总的来说， 拟议的研究将解决葡萄球菌如何与皮肤结合，结合什么配体，从而可能揭示 病原体和宿主之间的新的串扰层，可能导致新的治疗方式 治疗葡萄球菌感染。

ABSTRACT The goal of this Multi-PI project is to understand how Staphylococcus spp. bind to the skin surface. Although S. aureus has the capability to cause significant disease in humans, most Staphylococcus spp. do not cause disease but instead act as commensals or mutualists and adhere to the skin surface providing beneficial aspects to the host. These benefits include inhibition of pathogen colonization by synthesis of unique antimicrobial compounds in addition to appropriate immune system development. However, we do not know how Staphylococcus spp adhere to skin. This application hypothesizes that species of staphylococci that colonize humans do so in a conserved manner via an Aap (or SasG in S. aureus) orthologue that binds corneocytes. Aap is a rod-like fibrillar protein that functions in initial adherence to corneocytes but also functions to mediate intercellular accumulation. To address this hypothesis, we have proposed the following specific aims: (1) understand the dynamics of Aap-mediated corneocyte adherence; (2) define the ligand specificity of Aap and SasG lectin domains and (3) investigate S. aureus SasG-dependent mechanisms of skin colonization. Overall, the proposed studies will address how staphylococci bind to skin, what ligand is bound, and thus could uncover new layers of crosstalk between pathogen and the host, potentially leading to novel therapeutic modalities for treating staphylococcal infections.