Metabolite sensing in a polymicrobial infection

项目摘要 许多细菌感染是由不同的微生物群落引起的。这些多菌感染通常 导致比单一物种感染更高的细菌负担和更严重的疾病，这种现象被称为 “协同效应”。虽然细菌之间的协同作用已经被认识到一个多世纪了，但分子机制 事实证明，这一事件的原因很难澄清。我的实验室一直专注于 条件致病菌Aggregatibacter放线菌(AA)与人类口腔共生 戈登氏链球菌(Sg)。在之前的赠款周期中，我们展示了AA/SG协同作用- 感染是由几个过程引起的，涉及AA对Sg代谢物L的利用和反应。 乳酸和过氧化氢。这次更新的目标有两个：1)确定AA-SG协同机制如何 我们已经发现了对环境干扰的影响稳健性，并精确地确定了空间 这些物种的组织影响感染期间的这种相互作用(具体目标1和2)；以及2)利用 高通量基因组学，以确定再生障碍性贫血和一系列联合感染之间发生的代谢相互作用 细菌(特定目标3)。

Project Summary Many bacterial infections are caused by diverse microbial communities. These polymicrobial infections often result in higher bacterial burdens and more severe disease than single-species infections, a phenomenon called “synergy”. While synergy between bacteria has been recognized for over a century, the molecular mechanisms that cause it have proven difficult to elucidate. My laboratory has focused on synergistic interactions between the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans (Aa) and the human oral commensal bacterium Streptococcus gordonii (Sg). In the previous grant cycle, we showed that synergy in Aa/Sg co- infections is caused by several processes involving Aa's utilization of, and response to, the Sg metabolites L- lactate and H2O2. The goal of this renewal is two-fold: 1) to determine how the Aa-Sg synergy mechanisms that we have discovered impact robustness to environmental disturbances and to determine precisely how the spatial organization of these species impacts such interactions during infection (Specific Aims 1 & 2); and 2) to utilize high-throughput genomics to define the metabolic interactions that occur between Aa and a range of co-infecting bacteria (Specific Aim 3).