Interactions of a commensal bacterium with the intestinal mucosal surface

共生细菌与肠粘膜表面的相互作用

• 批准号: 8003030
• 负责人: Breck A Duerkop
• 金额: $ 4.76万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003030
• 关键词: Bacteremia; Bacteria; Benign; Characteristics; Complex; Cues; Data; Development; Diet; Disease; Endocarditis; Enterococcus faecalis; Gene Expression; Genes; Genetic; Health; Hospitals; Human; Immune response; Inflammatory Bowel Diseases; Inflammatory Response; Intestines; Invaded; Lead; Life Style; Light; Metabolic; Metabolism; Molecular; Opportunistic Infections; Organism; Physiological; Polysaccharides; Predisposing Factor; Research; Sepsis; Surface; Therapeutic; base; commensal microbes; member; microbial community; novel; pathogen; public health relevance

DESCRIPTION (provided by applicant): The human intestine harbors nearly 100 trillion bacteria that are essential for health. These organisms make critical contributions to human metabolism by helping to break down complex polysaccharides that are ingested as part of the diet. However, certain members of this microbial community can invade the intestinal barrier and cause opportunistic infections that can lead to bacteremia and sepsis. Further, they can trigger detrimental inflammatory responses, leading to inflammatory bowel disease. However, little is known about what factors predispose normal intestinal bacteria to transition from benign symbionts to invasive pathogens. Enterococcus faecalis is a predominant member of the mammalian intestinal microbiota that can opportunistically disseminate from the intestine and cause disease. It is one of the most common causes of hospital-acquired bloodstream infections and is a major cause of endocarditis. The research outlined in this proposal will uncover the molecular factors that promote the transition from a symbiotic to a pathogenic lifestyle in E. faecalis. Based on preliminary data, one of the key factors governing this transition is environmental cues that are encountered by the organism when it attaches to the surface of the intestinal tract. This proposal will 1) Determine which environmental cues alter E. faecalis gene expression during association with the intestinal surface; 2) Identify E. faecalis genes that are important for attachment to and invasion of the intestinal barrier; and 3) Determine how the host immune response minimizes E. faecalis attachment to and invasion of the intestinal barrier. These studies should shed light on the mechanisms used by bacteria to transition from a commensal lifestyle to a pathogenic state in the host. Furthermore, these studies will likely identify candidate targets for the development of novel IBD therapeutics and treatments for opportunistic infections. PUBLIC HEALTH RELEVANCE: Intestinal commensal bacteria typically establish symbiotic relationships with their human hosts, making critical contributions to metabolic health. However, Enterococcus faecalis is an intestinal commensal that can become an opportunistic pathogen and is one of the most common causes of bacteremia and endocarditis in humans. This proposal aims at discovering the genetic and physiological characteristics of E. faecalis that promotes its transition from a symbiont to a pathogen.

描述（由申请人提供）：人体肠道中有近100万亿个对健康至关重要的细菌。这些生物通过帮助分解作为饮食一部分摄入的复杂多糖，对人体新陈代谢做出了重要贡献。然而，这种微生物群落的某些成员可以侵入肠道屏障并引起机会性感染，从而导致菌血症和败血症。此外，它们还会引发有害的炎症反应，导致炎症性肠病。然而，对于哪些因素易使正常肠道细菌从良性共生体转变为侵袭性病原体，人们知之甚少。粪肠球菌是哺乳动物肠道微生物群的主要成员，可以机会性地从肠道传播并引起疾病。它是医院获得性血流感染的最常见原因之一，也是心内膜炎的主要原因。本提案中概述的研究将揭示促进粪肠杆菌从共生到致病生活方式转变的分子因素。根据初步数据，控制这种转变的关键因素之一是生物体附着在肠道表面时遇到的环境线索。该研究将1)确定哪些环境因素会改变粪肠球菌基因在肠道表面的表达；2)确定粪肠杆菌附着和侵入肠道屏障的重要基因；3)确定宿主免疫反应如何最大限度地减少粪肠杆菌对肠道屏障的附着和入侵。这些研究应该阐明细菌在宿主体内从共生生活方式过渡到致病状态的机制。此外，这些研究可能会确定开发新的IBD治疗方法和治疗机会性感染的候选靶点。