Genetic determinants of bacterial fitness 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，导致感染部位的定植、持久性和抗生素耐药性增强。这种相互作用在多菌性软组织感染中尤其明显，例如在 烧伤和慢性伤口，尽管控制这些协同作用的分子过程一般不为人所知。研究阐明有助于提高体内持久性的多微生物相互作用所涉及的遗传路径，对于全面了解协同作用至关重要，也是开发治疗多物种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基因组的角度检查机会性病原体之间的相互作用如何影响急性和慢性伤口感染的体内持久性。为了实现这一目标，高通量基因组学技术将被用来识别在多菌协同过程中所需和表达的微生物基因。

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, persistence and antibiotic resistance in the infection site. Such interactions have been particularly noted in polymicrobial soft tissue infections, such as those in burns and chronic wounds, although the molecular processes controlling these synergistic interactions are generally not known. Studies elucidating the genetic pathways involved in polymicrobial interactions that contribute to enhanced persistence in vivo is critical for a comprehensive understanding of synergy, and a necessary first step towards developing therapeutics to treat multi-species infections. The overall goal of this research plan is to examine, from a genomic standpoint, how interactions between opportunistic pathogens impact in vivo persistence in acute and chronic wound infections. To accomplish this goal, high-throughput genomics techniques will be employed to identify microbial genes that are required for and expressed during polymicrobial synergy.