C ALBICANS IN THE GI TRACT ENVIRONMENT

胃肠道环境中的白色念珠菌

• 批准号: 9765139
• 负责人: CAROL A. KUMAMOTO
• 金额: $ 50.51万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765139
• 关键词: Adherence; Adverse effects; Affect; Antibiotics; Back; Benign; Blood; Candida albicans; Catechols; Cells; Clostridium difficile; Communities; Development; Dioxygenases; Disease; Disease susceptibility; Enteral; Environment; Enzymes; Epithelial Cells; Epithelium; Event; Gastrointestinal tract structure; Gene Expression; Genes; Goals; Health; Health Promotion; Host resistance; Human; Immune response; Immunocompromised Host; Individual; Infection; Intervention; Knowledge; Learning; Light; Measures; Metabolic; Microbe; Modeling; Molecular; Mus; Organism; Oxidative Stress; Patients; Play; Population; Predisposition; Prevention; Proteins; Reactive Oxygen Species; Recombinant DNA; Recovery; Research; Research Project Grants; Resistance; Role; Stream; Superoxide Dismutase; Testing; Time; antimicrobial; base; biological adaptation to stress; commensal bacteria; fungus; gut colonization; gut microbiota; host colonization; host microbiota; improved; member; metabolome; metabolomics; microbial; microbial community; microbiota; microorganism; mutant; novel; pathogen; pathogenic bacteria; reconstitution; response; transcription factor

This research project investigates the interactions between colonizing Candida albicans cells and the GI tract environment. GI colonization with C. albicans is common for humans and generally does not have adverse effects on human health. However, if a patient becomes immunocompromised, colonizing C. albicans cells can escape the GI tract, reach the blood stream and cause disseminated disease. GI colonization is therefore significant because disease-causing fungal cells arise from the populations that colonize the host as harmless commensals. In addition, preliminary results show that, under certain conditions, colonization with C. albicans increases the resistance of the host to lethal challenge with an enteric bacterial pathogen. The long term goals of the proposed research are to understand the mechanisms by which C. albicans alters the GI tract environment and affects host resistance to challenge. The focus of Specific Aim 1 is to identify C. albicans activities that detoxify antimicrobial compounds. In Specific Aim 2, the goal is to understand how C. albicans alters the metabolite milieu of the GI tract. The studies proposed in Specific Aim 3 will analyze the effects of C. albicans colonization on the composition of the gut microbiota. These studies will increase the understanding of the interplay between C. albicans and the mammalian GI tract environment. Deeper understanding will enable development of novel interventions that harness the beneficial effects of C. albicans in the GI tract.

本研究项目探讨定植白色念珠菌细胞与胃肠道环境之间的相互作用。白色念珠菌在胃肠道定植是人类常见的，通常不会对人类健康产生不利影响。然而，如果患者免疫功能受损，定植的白色念珠菌细胞可以逃离胃肠道，进入血液并引起弥散性疾病。因此，胃肠道定植具有重要意义，因为致病真菌细胞起源于定植宿主的无害共生体种群。此外，初步结果表明，在一定条件下，白色念珠菌的定植增加了宿主对肠道细菌病原体致命挑战的抵抗力。该研究的长期目标是了解白色念珠菌改变胃肠道环境和影响宿主抵抗挑战的机制。特异性目标1的重点是鉴定白色念珠菌解毒抗菌化合物的活性。在特异性目标2中，目标是了解白色念珠菌如何改变胃肠道的代谢物环境。在Specific Aim 3中提出的研究将分析白色念珠菌的作用