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: 8096562
• 负责人: Breck A Duerkop
• 金额: $ 5.13万
• 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/8096562
• 关键词: Adopted; Adult; Antibodies; Antibody-mediated protection; Antigens; Apoptosis; Apoptotic; B cell differentiation; B-Lymphocytes; Bacteremia; Bacteria; Benign; Cell Cycle; Cell Cycle Arrest; Cell Survival; Cell surface; Cells; Characteristics; Complex; Cues; Data; Development; Diet; Disease; Endocarditis; Enterococcus faecalis; Exhibits; Frequencies; Gene Expression; Genes; Genetic; Goals; Health; Hepatitis B Vaccines; Hospitals; Human; Immune response; Immunity; Immunization; Immunoglobulin-Secreting Cells; Inflammatory Bowel Diseases; Inflammatory Response; Intestines; Invaded; Lead; Life; Life Style; Light; Lymphocyte; Mediating; Memory; Memory B-Lymphocyte; Metabolic; Metabolism; Molecular; Opportunistic Infections; Organism; Persons; Phenotype; Physiological; Plasma Cells; Polysaccharides; Predisposing Factor; Proliferating; Property; Research; Secondary to; Sepsis; Surface; Techniques; Testing; Tetanus Toxoid; Therapeutic; Time; Up-Regulation; Vaccination; Vaccines; base; commensal microbes; design; experience; improved; inhibitor/antagonist; innovation; member; microbial community; novel; pathogen; programs; response

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.

描述(申请人提供)：人体肠道中含有近100万亿种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，对人类的新陈代谢做出了关键贡献。然而，这种微生物群落的某些成员可以入侵肠道屏障，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，人们对哪些因素使正常肠道细菌从良性共生体转变为侵袭性病原体知之甚少。粪肠球菌是哺乳动物肠道微生物区系中的主要成员，可从肠道有机会传播并导致疾病。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。这项提案中概述的研究将揭示促进粪肠球菌从共生生活方式向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有机体附着在肠道表面时遇到的环境线索。这项建议将1)确定哪些环境线索改变了粪肠球菌在与肠道表面相关的过程中的基因表达；2)确定了粪肠球菌对肠道屏障的附着和入侵至关重要的基因；以及3)确定了宿主免疫反应如何将粪肠球菌对肠道屏障的附着和入侵降至最低。这些研究应该能揭示细菌在宿主中从共生生活方式转变为致病状态所使用的机制。此外，这些研究可能会确定开发新的IBD疗法和治疗机会性感染的候选靶点。