Metabolite sensing in a polymicrobial infection

多种微生物感染中的代谢物传感

• 批准号: 10213693
• 负责人: Marvin Whiteley
• 金额: $ 36.38万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213693
• 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

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 许多细菌感染是由潜水微生物群落引起的。这些多数菌感染经常 与单物种感染相比，导致伯良细菌更高，疾病更严重，这种现象称为 “协同作用”。虽然细菌之间的协同作用已识别为一个多世纪，但分子机制 事实证明，这很难阐明。我的实验室专注于协同互动 机会性口腔病原体聚集术，放线菌（AA）和人类的口服 细菌Gordonii（SG）。在上一个赠款周期中，我们显示了AA/SG共同的协同作用 感染是由几个过程引起的，涉及AA对SG代谢物L-的利用和反应引起的。 缝合和H2O2。这种续订的目标是两倍：1）确定AA-SG协同机制如何 我们发现了对环境灾难的影响鲁棒性，并确定空间如何 这些物种的组织会影响感染期间这种相互作用（特定目的1和2）； 2）使用 高通量基因组学来定义AA和一系列共同感染之间发生的代谢相互作用 细菌（特定目标3）。