Probing polymicrobial synergy using high throughput genomics

描述(申请人提供)：大多数细菌发病机制研究都集中在单一培养感染上；然而，很明显，许多细菌感染并不是单一物种定居的简单结果，而是多个微生物群落作用的结果。多菌感染中的微生物通常表现出协同作用，导致感染部位更强的定植和持久性。这种相互作用在口腔感染中尤其明显，尽管控制这些协同作用的分子过程通常尚不清楚。详细的机制研究阐明了增强体内持久性所必需的多微生物相互作用，对于全面了解协同作用至关重要，也是开发治疗多微生物感染的治疗方法的必要第一步。这项研究计划的总体目标是从机械学的角度检查口腔细菌之间的相互作用如何影响群落发展和体内的持久性。为了实现这一目标，将利用高通量基因组学技术来鉴定在联合感染过程中唯一表达和/或多菌协同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.