Mechanisms of Pseudomonas aeruginosa virulence in polymicrobial wound infections

 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。这种相互作用在伤口感染中尤其明显，尽管控制这些协同作用的分子过程通常尚不清楚。对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治疗方法的必要的第一步。这项研究计划的总体目标是确定铜绿假单胞菌和其他通常合并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，将利用体内小鼠创伤模型和高通量基因组学技术来鉴定和表征在联合感染过程中增强致病作用所需的微生物基因。

 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.