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Niche Establishment by Bacteroides fragilis - Resubmission 01

脆弱拟杆菌的生态位建立 - 重新提交 01

基本信息

批准号：
9329228
负责人：
Benjamin Casterline
金额：
$ 4.9万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9329228
关键词：
Ablation Address Adult American Anaerobic Bacteria Antibiotic Therapy Antibiotics Bacteria Bacteroides Bacteroides fragilis Bacteroides fragilis toxin Bacteroides thetaiotaomicron Benign Carbohydrates Cessation of life Chronic Colitis Colon Colon Carcinoma Diarrhea Dietary Polysaccharide Disease E-Cadherin Enteral Epithelial Family Gene Cluster Genetic Genetic Transcription Genome Gnotobiotic Gram-Negative Bacteria Homeostasis Human Human Milk Immune Immune signaling Immunity Impairment In Situ In Vitro Infant Infection Inflammatory Bowel Diseases Injury Integration Host Factors Intestines Life Light Adaptations Link Lipid A Lipopolysaccharides Malnutrition Metabolism Metalloproteases Microbe Modeling Molecular Mucins Mucolytics Mucous body substance Mus Names Neonatal Nosocomial Infections Nutrient Operative Surgical Procedures Outcome Pathogenesis Pathogenicity Pathway interactions Peptide Hydrolases Phosphoric Monoester Hydrolases Plants Polysaccharides Population Prevention Repression Role Sepsis Signal Pathway Starch Symbiosis System Testing Toxin Vertical Disease Transmission Virulence Factors Weaning Work antimicrobial peptide derepression fragilysin germ free condition homeobox protein PITX1 host-microbe interactions immunogenic in vivo insight microbiota mouse model mutualism novel overexpression pathogen prevent protein degradation sugar trait

项目摘要

Project Summary Maternally acquired microbes may predispose to disease later in life; however, the determinants of niche establishment and their contributions to disease are poorly understood. We have developed a mouse model of vertical transmission in which the common human commensal enterotoxigenic Bacteroides fragilis (ETBF), carried by the dam, is stably established in the neonatal microbiota. Surprisingly, Bacteroides fragilis toxin (BFT), a carbohydrate-regulated metalloprotease associated with E-cadherin cleavage, is a key determinant of maternal inheritance, as BFT-deficient ETBF shows impaired persistence in weaned mice. Enteric disease in adulthood can be induced by antibiotics and is characterized by ETBF outgrowth, elevated bft expression, and loss of colonic mucus. We propose a model in which antibiotic treatment favors expansion of the mucolytic ETBF population and depletion of mucus-associated sugars, leading to bft derepression and host injury.

项目摘要母体获得的微生物可能在以后的生命中易患疾病；然而，生态位的决定因素其建立及其对疾病的贡献还知之甚少。我们已经开发了一种小鼠模型在垂直传播中，常见的人类共生产肠毒素脆弱类杆菌(ETBF)，由水坝携带，稳定地建立在新生儿的微生物区系中。令人惊讶的是，脆弱类杆菌毒素 (BFT)是一种与E-钙粘蛋白切割相关的碳水化合物调节的金属蛋白酶，是决定E-钙粘素活性的关键因素。母系遗传，因为BFT缺陷的ETBF在断奶小鼠中表现出持久性受损。肠道疾病成年期可由抗生素诱导，其特征是ETBF生长，BFT表达升高，以及结肠粘液丢失。我们提出了一个模型，在这个模型中，抗生素治疗有利于粘液溶解的扩大。 ETBF种群和粘液相关糖的耗尽，导致BFT去抑制和宿主损伤。