Molecular characterization of mixed-species bacterial biofilms in the gastrointestinal tract

胃肠道中混合物种细菌生物膜的分子特征

• 批准号: RGPIN-2015-05243
• 负责人: Walter, Jens
• 金额: $ 3.28万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689030
• 关键词: Molecular; characterization; mixed; species; bacterial

The gut microbiota (the community of microbes that colonizes the gastrointestinal tract) plays important roles in human health and disease, but little is known about the basic principles that underlie host-microbial symbiotic interactions in the vertebrate gut. In particular, the interactions between the bacterial members of multi-species intestinal biofilms have not been studied at all, but such knowledge is essential for the development of strategies that modulate the gut microbiota to improve health. Capitalizing on gnotobiotic mice (mice with a defined microbiota), the applicant's group has developed a unique model by which to disentangle the bacterial functions that contribute to biofilm formation in the gastrointestinal tract. Using this model, we have demonstrated that selective biofilm formation in the mouse stomach as a key mechanism by which host specificity is facilitated in the species Lactobacillus reuteri, and have begun to elucidate the molecular processes that underlie formation of biofilms. However, we know little about how these biofilms function and evolve in the context of the mixed species populations that occur in nature. ******The long-term objective of this research program is to identify the mechanisms by which multi-species Lactobacillus biofilms evolved and function, and characterize the interactions between the individual members on a molecular level. In the proposed study, we will use an innovative combination of experiments with mice that harbor defined Lactobacillus populations and genomic approaches to specifically identify bacterial interactions among mixed-species biofilms in the intestinal tract. The project is innovative in that it uses Lactobacillus isolates that coexisted in the gut of wild mice, a powerful genomic approach (transposon sequencing) that allows the identification of relevant genes directly in the environment, and an experimental model (gnotobiotic mice) that allow to study gene function in real-life ecological context. The experiments are therefore likely to identify genes that contribute to bacterial biofilms that have not been described so far.******The benefit to the research field and Canada: The work will likely provide unprecedented insight into the mechanisms by which mixed-species bacterial biofilms in nature are established and how the members evolve, and it is likely to discover novel processes that remain elusive in other models of biofilms. The findings have the potential to provide the basis for strategies to modulate biofilms with both beneficial and detrimental roles in human and animal health. The project will train six HQP, three of which have citizenship or permanent residency in Canada, and will provide a unique interdisciplinary experience that makes them uniquely qualified to contribute to progress in the gut microbiome field (a field that is currently considered one of the frontiers in biology and medicine).

肠道微生物群（在胃肠道定植的微生物群落）在人类健康和疾病中起着重要作用，但对脊椎动物肠道中宿主-微生物共生相互作用的基本原理知之甚少。特别是，多物种肠道生物膜的细菌成员之间的相互作用尚未得到研究，但这些知识对于制定调节肠道微生物群以改善健康的策略至关重要。利用gnotobiotic小鼠（具有确定的微生物群的小鼠），申请人的小组已经开发了一种独特的模型，通过该模型来解开有助于胃肠道中生物膜形成的细菌功能。使用这个模型，我们已经证明，选择性的生物膜形成在小鼠胃作为一个关键的机制，宿主特异性是促进物种罗伊氏乳杆菌，并已开始阐明的分子过程，形成生物膜的基础。然而，我们对这些生物膜如何在自然界中发生的混合物种种群的背景下发挥作用和进化知之甚少。* 本研究计划的长期目标是确定多物种乳酸菌生物膜进化和功能的机制，并在分子水平上表征单个成员之间的相互作用。在这项拟议的研究中，我们将使用一种创新的实验组合，用含有确定的乳杆菌种群的小鼠和基因组方法来特异性地识别肠道中混合物种生物膜之间的细菌相互作用。该项目具有创新性，因为它使用了野生小鼠肠道中共存的乳酸杆菌分离株，一种强大的基因组方法（转座子测序），可以直接在环境中识别相关基因，以及一种实验模型（gnotobiotic小鼠），可以在现实生活中研究基因功能生态环境。因此，这些实验可能会识别出迄今为止尚未描述的细菌生物膜的基因。对研究领域和加拿大的好处：这项工作可能会对自然界中混合物种细菌生物膜的建立机制以及成员如何进化提供前所未有的见解，并且可能会发现在其他生物膜模型中仍然难以捉摸的新过程。这些发现有可能为调节生物膜的策略提供基础，这些生物膜对人类和动物健康既有利又有害。该项目将培训六名HQP，其中三名拥有加拿大公民身份或永久居留权，并将提供独特的跨学科经验，使他们有资格为肠道微生物组领域的进步做出贡献（该领域目前被认为是生物学和医学的前沿领域之一）。