Structural basis for mobilization of S. aureus pathogenicity islands

项目总结 金黄色葡萄球菌是一种条件致病菌，与严重感染有关。 人类。金黄色葡萄球菌中的大多数毒力决定因素是由可移动的遗传元件携带的 (MGES)，如质粒、噬菌体和基因组岛。转导由 噬菌体是MGES传播的主要机制 在金黄色葡萄球菌中水平分布。其中包括金黄色葡萄球菌致病岛(SaPI)， 这些病毒携带编码超抗原毒素和其他毒力因子的基因。SaPI通常是 稳定地整合到宿主基因组中，但通过特定的 辅助噬菌体，导致将SAPI基因组包装成转导颗粒 来自辅助者编码的结构蛋白。SaPI已经进化出感知存在的能力 利用噬菌体功能并干扰噬菌体增殖，以便 促进自身的传播。这是否在金黄色葡萄球菌的进化过程中起着重要作用 致病性。 当前项目的总体目标是了解SAPI的结构基础 动员，帮助者-SAPI的特异性，以及在其传播和建立过程中涉及的因素。 我们的具体目标是：(1)确定SAPI诱导衣壳大小重定向的机制；(2) 了解噬菌体基板在感染和宿主特异性中的作用；(3)阐明 次要衣壳蛋白gp44在裂解/溶源转换中的作用。 这三个目标侧重于动员进程的不同方面，并将加以研究 通过遗传、生化和结构方法的组合。所有这三个目标都基于 我们之前的研究和广泛的初步数据设定了坚实的前提。在完成后 这些目标，我们将获得对衣壳组装和大小过程的新见解 重定向，感染和传播过程，SaPI和他们的 毒力因子在细菌群体中传播和确立。

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.