Mechanisms of Pseudomonas aeruginosa virulence in polymicrobial wound infections

 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，而是由多种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。这种相互作用在伤口感染中特别明显，尽管控制这些协同相互作用的分子过程通常是未知的。增强体内持久性所需的多微生物相互作用的详细机制研究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确定铜绿假单胞菌和其他通常共同感染伤口的微生物之间的相互作用如何影响伤口严重程度。为了实现这一目标，将采用体内小鼠伤口模型和高通量基因组学技术来鉴定和表征在共感染期间增强发病机制所需的微生物基因。

 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 wound infections, although the molecular processes controlling these synergistic interactions are generally not known. Detailed mechanistic studies of the polymicrobial interactions required for enhanced persistence in vivo are a necessary first step towards developing therapeutics to treat polymicrobial infections. The overall goal of this research plan is to determine how interactions between Pseudomonas aeruginosa and other microbes that commonly co-infect wounds impact wound severity. To accomplish this goal, in vivo murine wound models and high-throughput genomics techniques will be employed to identify and characterize microbial genes required for enhanced pathogenesis during co-infection.