Structural basis for mobilization of S. aureus pathogenicity islands

项目摘要 金黄色葡萄球菌是一种机会致病菌， 人类大多数毒力决定因子在S.金黄色葡萄球菌携带在移动的遗传元件上 在一些实施方案中，所述方法包括将所述多个微生物体（MGE），如质粒、噬菌体和基因组岛（genomic islands）结合。转导 噬菌体（Bacteriophage，EGE）是MGE传播的主要机制 在S水平。金黄色。这些MGE中有S。金黄色葡萄球菌致病岛（SaPI）， 其携带编码超抗原毒素和其它毒力因子的基因。SAPI通常 稳定整合到宿主基因组中，但被特异性的 辅助病毒，导致SaPI基因组包装到转导颗粒中， 辅助编码的结构蛋白。智能感知者已经进化出了感知 利用噬菌体功能并干扰噬菌体增殖， 促进自己的传播。这在S.金黄色葡萄球菌的进化和 致病性 本项目的总体目标是了解SaPI的结构基础 动员，辅助SaPI特异性，以及参与其传播和建立的因素。 我们的具体目标是：（1）确定SaPI诱导的衣壳大小重定向的机制;（2） 了解噬菌体底板在感染和宿主特异性中的作用;（3）阐明噬菌体底板的作用机制 次要衣壳蛋白GP 44在溶解/溶原转换中的作用。 这三个目标侧重于动员过程的不同方面， 通过遗传学、生物化学和结构学方法的结合。这三个目标都是基于 我们以前的研究和广泛的初步数据建立了坚实的前提。完成后 这些目标，我们将获得新的见解的过程中，衣壳组装和大小 重定向，感染和转移过程，SaPI及其 毒力因子在细菌群体中传播和建立。

PROJECT SUMMARY Staphylococcus aureus is an opportunistic bacterial pathogen involved in severe infections in humans. Most virulence determinants in S. aureus are carried on mobile genetic elements (MGEs), such as plasmids, bacteriophages and genomic islands. Transduction by bacteriophages (phages) represents the main mechanism by which MGEs are transmitted horizontally in S. aureus. Among these MGEs are the S. aureus pathogenicity islands (SaPIs), which carry genes encoding superantigen toxins and other virulence factors. SaPIs are normally stably integrated into the host genome, but become mobilized at high frequency by specific helper phages, resulting in packaging of the SaPI genomes into transducing particles made from helper-encoded structural proteins. SaPIs have evolved the ability to sense the presence of a lytic phage, exploit phage functions and interfere with phage multiplication, in order to promote their own dissemination. SaPIs this play important roles in S. aureus evolution and pathogenicity. The overall aim of the current project is to understand the structural basis for SaPI mobilization, helper-SaPI specificity, and the factors involved in their spread and establishment. Our specific aims are: (1) Determine the mechanism of SaPI-induced capsid size redirection; (2) Understand the function of the phage baseplate in infection and host specificity; (3) Elucidate the role of minor capsid protein gp44 in the lytic/lysogenic switch. These three aims focus on different aspects of the mobilization process and will be studied by a combination of genetic, biochemical and structural methods. All three aims are based on a solid premise set by our previous studies and extensive preliminary data. Upon completion of these aims, we will have gained new insights into the process of capsid assembly and size redirection, the infection and transfer process, the mechanisms by which SaPIs and their virulence factors are transmitted and established in the bacterial population.