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: 8296343
• 负责人: Breck A Duerkop
• 金额: $ 5.39万
• 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/8296343
• 关键词: Adherence; Bacteremia; Bacteria; Bacterial Physiology; Benign; Characteristics; Communities; Complex; Cues; DNA Microarray Chip; Data; Development; Diet; Disease; Endocarditis; Enterococcus faecalis; Event; Exhibits; Gene Expression; Genes; Genetic; Genetic Determinism; Germ-Free; Gnotobiotic; Goals; Gram-Positive Bacteria; Health; Hospitals; Human; Immune; Immune response; Immunity; Inflammatory Bowel Diseases; Inflammatory Response; Intestines; Invaded; Knockout Mice; Lead; Lectin; Life Style; Light; Metabolic; Metabolism; Modeling; Molecular; Mucous Membrane; Mus; Natural Immunity; Opportunistic Infections; Organism; Outcome; Pathology; Physiological; Physiological Adaptation; Polysaccharides; Predisposing Factor; Reporter Genes; Research; Role; Sepsis; Surface; Technology; Therapeutic; Time; Tissues; Virulence; antimicrobial; base; commensal microbes; in vivo; insight; member; microbial community; microbial host; mouse model; novel; pathogen

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.

人体肠道内有近100万亿个对健康至关重要的细菌。这些生物体通过帮助分解作为饮食的一部分摄入的复杂多糖，对人体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，它们还可能引发有害的炎症反应，导致炎症性肠病。然而，很少有人知道是什么因素使正常的肠道细菌从良性共生菌转变为侵入性病原体。粪肠球菌是哺乳动物肠道微生物群的主要成员，其可以从肠道机会性传播并引起疾病。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。这项研究概述了这项建议将揭示分子因素，促进从共生转变为致病的生活方式在E。粪便。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。该建议将1）确定哪些环境线索改变E。faecalis基因在与肠表面结合过程中的表达; 2）鉴定E. faecalis的基因，这些基因对于附着和侵入肠屏障是重要的;和3）确定宿主免疫应答如何最小化E.粪便附着并侵入肠屏障。这些研究应该阐明细菌在宿主中从寄生生活方式转变为致病状态的机制。此外，这些研究将可能确定用于开发新的IBD疗法和治疗机会性感染的候选靶点。