Identification and characterization of competition-factors of commensal E. coli and their role in inhibition of enteropathogens in the inflamed intestine

共生大肠杆菌竞争因子的鉴定和表征及其在抑制发炎肠道中肠道病原体中的作用

• 批准号: 189797391
• 负责人: Professorin Dr. Barbara Stecher
• 金额: --
• 依托单位: Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/189797391?language=en
• 关键词: Identification; characterization; competition; factors; commensal

Gastrointestinal infections are a major global health problem claiming 1.8 million lives per year according to the WHO. The commensal microflora, populating the intestine to high levels, con-tributes to protection against these infections. Inflammation, induced by enteric pathogens des-tabilizes the normal microbiota by so far poorly understood mechanisms and leads to pathogen overgrowth. So far, it has been assumed that only pathogens (i.e. Salmonella enterica spp.I serovar Typhimurium) can benefit from intestinal inflammation. However, we have recently ob-served that certain E. coli strains (i.e. commensal mouse isolate E. coli 8178) in contrast to oth-ers (i.e. E. coli Nissle) can out-compete Salmonella Typhimurium in a mouse colitis model. In the proposed project we plan to investigate the molecular mechanisms of competitive E. coli overgrowth and pathogen suppression in the inflamed gut. We aim at identifying traits that con-tribute to the competitive phenotype of E. coli 8178 (= 'competition-genes') but are absent in E. coli Nissle by using two independent genetic screening approaches. We will analyze the distri-bution of 'competition-genes' within the E. coli pangenome and address their regulation in re-sponse to in vivo stimuli. The results will enhance our understanding of the role of competitive E. coli in enteropathogen infection and may be exploited for the improvement of probiotics in the future.

胃肠道感染是一个主要的全球性健康问题，根据世界卫生组织，每年夺去180万人的生命。肠道微生物菌群在肠道内大量繁殖，有助于预防这些感染。由肠道病原体诱导的炎症通过迄今为止知之甚少的机制使正常微生物群失稳，并导致病原体过度生长。到目前为止，人们认为只有病原体（即肠道沙门氏菌I血清型鼠伤寒沙门氏菌）才能从肠道炎症中受益。然而，我们最近观察到，某些E.大肠杆菌菌株（即E.coli小鼠分离株E. coli8178），而E. coli Nissle）可以在小鼠结肠炎模型中胜过鼠伤寒沙门氏菌。 本研究拟探讨竞争性E.大肠杆菌过度生长和病原体抑制在发炎的肠道。我们的目标是鉴定有助于E. coli8178（=“竞争基因”），但在大肠杆菌中不存在。coli Nissle中进行遗传筛选。我们将分析“竞争基因”在E.大肠杆菌泛基因组的研究，并探讨其在体内刺激反应中的调控。这一结果将加深我们对竞争性E.大肠杆菌在肠道病原菌感染中的作用，可用于未来益生菌的改进。

项目成果

Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae

• DOI: 10.1073/pnas.1113246109
• 发表时间: 2012-01-24
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Stecher, Baerbel;Denzler, Remy;Hardt, Wolf-Dietrich
• 通讯作者: Hardt, Wolf-Dietrich