Probing polymicrobial synergy using high throughput genomics

描述（由申请人提供）：大多数细菌发病机制研究集中在单一培养物感染;然而，很明显，许多细菌感染不仅仅是单一菌种定植的结果，而是由多微生物群落的作用引起的。多微生物感染中的微生物通常显示协同相互作用，导致感染部位的定植和持久性增强。这种相互作用在口腔感染中特别明显，尽管控制这些协同相互作用的分子过程通常是未知的。阐明增强体内持久性所必需的多微生物相互作用的详细机制研究对于全面理解协同作用至关重要，并且是开发治疗多微生物感染的疗法的必要的第一步。本研究计划的总体目标是从机理的角度研究口腔细菌之间的相互作用如何影响群落发育和体内持久性。为了实现这一目标，将采用高通量基因组学技术来鉴定在共感染期间独特表达和/或多微生物协同作用所需的微生物毒力基因。

DESCRIPTION (provided by applicant): Most bacterial pathogenesis studies have focused on mono-culture infections; however, it is clear that many bacterial infections are not simply the result of colonization with a single species, but rather ensue from the action of polymicrobial communities. Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization and persistence in the infection site. Such interactions have been particularly noted in infections of the oral cavity, although the molecular processes controlling these synergistic interactions are generally not known. Detailed mechanistic studies elucidating the polymicrobial interactions necessary for enhanced persistence in vivo is critical for a comprehensive understanding of synergy, and a necessary first step towards developing therapeutics to treat polymicrobial infections. The overall goal of this research plan is to examine, from a mechanistic standpoint, how interactions between oral bacteria impact community development and in vivo persistence. To accomplish this goal, high-throughput genomics techniques will be employed to identify microbial virulence genes that are uniquely expressed during co-infection and/or required for polymicrobial synergy.