Contact-dependent interbacterial responses modulate intestinal colonization by Bacteroides species

接触依赖性细菌间反应调节拟杆菌属的肠道定植

• 批准号: 10434773
• 负责人: Dustin E Bosch
• 金额: $ 16.15万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-18 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10434773
• 关键词: Affect; Anatomy; Applications Grants; Bacteria; Bacteriology; Bacteroides; Bacteroides fragilis; Bacteroides thetaiotaomicron; Bacteroidetes; Board Certification; Carbohydrates; Cells; Clinical; Clinical Pathology; Coculture Techniques; Communication Research; Communities; Complex; DNA; Development; Development Plans; Diet; Disease; Doctor of Medicine; Doctor of Philosophy; Ecosystem; Educational workshop; Elements; Environment; Faculty; Funding; Genome; Germ-Free; Gnotobiotic; Goals; Grant; Growth; Human; Immunity; Individual; Intestines; K-Series Research Career Programs; Lateral; Leadership; Link; Mannans; Mediating; Mentored Clinical Scientist Development Award (K08); Mentorship; Microbiology; Molecular; Mus; Pathology; Physicians; Polysaccharides; Process; Proteins; Proteomics; Research; Research Infrastructure; Research Personnel; Resource Development; Role; Scientist; Shapes; Starch; Structural Protein; System; Technology; Testing; Therapeutic; Toxin; Training; Translating; Transmembrane Transport; United States National Institutes of Health; Writing; Yeasts; antagonist; bacterial genetics; base; career; career development; cell behavior; experimental study; gastrointestinal; gut colonization; gut microbiota; human disease; meetings; microbiota; mouse model; novel; nuclease; professor; response; skills; symbiont; targeted treatment

Project Summary/Abstract The diverse group Bacteroidales is a predominant component of human intestinal microbiota, linked to numerous disease processes. Manipulation of Bacteroidales at the genus and species level holds therapeutic potential, but requires a more detailed understanding of the intestinal ecosystem. Bacteroides spp. genomes encode polysaccharide utilization loci (PUL), allowing enzymatic breakdown, membrane transport, and utilization of complex carbohydrates. Bacteroides spp. antagonize one another within the intestinal environment by delivering toxic effectors via contact-dependent type VI secretion systems (T6SS), resulting in altered capacities for colonization and persistence. The central hypothesis of this proposal is that contact among Bacteroides spp. results in dynamic adaptive responses that alter cellular behavior and contribute to persistence in the intestinal environment. The proposed experiments will discover contact-dependent proteomic responses important for competition within Bacteroides communities using cutting-edge proteomics technology (Aim 1). Molecular mechanisms of two known contact-dependent responses, altered polysaccharide utilization (Aim 2) and T6SS- mediated delivery of hcp-effector fusions (Aim 3), will be elucidated and translated to competitive growth and intestinal colonization in a gnotobiotic mouse model. A long-term research goal is to understand mechanisms underlying interbacterial interactions among intestinal symbionts for the development of targeted therapeutics. The candidate for this career development award is an M.D./Ph.D. physician scientist with board certification in anatomic and clinical pathology. The research proposed in this grant application will be conducted under the mentorship of Dr. Joseph Mougous, Professor of Microbiology, and Dr. Matthew Yeh, Professor of Pathology. The candidate will join faculty in a department with ample clinical resources for development of specialized expertise in gastrointestinal pathology, established NIH-funded investigators and research infrastructure, and a track record of strong support for physician scientists. The candidate is committed to a career as a physician scientist and seeks further scientific training. Career development plans include participation in relevant local and national meetings, advanced didactics and workshops to gain expertise in commensal bacteriology, build research communication and grant writing skills, and develop leadership and management skills. This mentored clinical scientist development award will facilitate the candidate’s transition to become a competitive NIH-funded independent investigator.

项目总结/文摘