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Metabolite sensing in a polymicrobial infection

多种微生物感染中的代谢物传感

基本信息

批准号：
10443703
负责人：
Marvin Whiteley
金额：
$ 35.98万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10443703
关键词：
3D Print Abscess Actinobacillus actinomycetemcomitans Antibiotics Bacteria Bacterial Infections Communities Complement Complex Cues Development Disease Disease Progression Future Genes Genetic Genomics Goals Grant Growth Human Hydrogen Peroxide Immune system In Situ In Vitro Infection Laboratories Lead Mediating Mediator of activation protein Metabolic Methods Microbe Molecular Oral Oral cavity Pathogenesis Pathway interactions Positioning Attribute Process Research Proposals Resistance Severity of illness Signal Transduction Site Streptococcus gordonii Structure Technology Testing Work bacterial fitness base biomaterial compatibility co-infection commensal bacteria confocal imaging fitness in vivo member microbial community novel therapeutic intervention oral commensal oral pathogen oral streptococci public health relevance resilience response synergism transposon sequencing

项目摘要

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).

项目摘要许多细菌感染是由不同的微生物群落引起的。这些多种微生物感染通常导致更高的细菌负担和更严重的疾病比单一物种感染，这种现象被称为 “协同”。虽然细菌之间的协同作用已经被认识了超过世纪，但分子机制这是很难解释的我的实验室专注于口腔条件致病菌伴放线菌聚集杆菌（Aggregatibacteractinomycetemcomitans，Aa）与人口腔黏膜炎格氏链球菌（Streptococcus gordonii，Sg）。在上一个资助周期中，我们发现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-的利用和响应。乳酸和H2 O2。该更新的目标是双重的：1）确定Aa-Sg如何协同机制，我们已经发现了对环境干扰的影响鲁棒性，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（具体目的1和2）;以及2）利用高通量基因组学来定义Aa和一系列共感染之间发生的代谢相互作用，细菌（具体目标3）。