The contribution of bacteriophages to host-microbe interactions in the intestine

噬菌体对肠道宿主-微生物相互作用的贡献

• 批准号: 9408038
• 负责人: Breck A Duerkop
• 金额: $ 10.07万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9408038
• 关键词: contribution; bacteriophages; host; microbe; interactions

DESCRIPTION (provided by applicant): The mammalian intestine is home to a dense community of bacteria that are integral to host health. Alterations in this bacterial population ca cause intestinal distress and even in some cases inflammatory disease. Aside from bacteria, viruses are also abundant in the intestinal tract. Both eukaryotic and prokaryotic viruses make up the intestinal "virome", however, viruses that infect bacteria, known as bacteriophages (phages), dominate. The majority of intestinal phages exist as lysogenic prophages that are stably integrated into bacterial chromosomes. Prophages typically undergo lytic induction to produce infectious phage particles when bacterial cells are stressed or when they are stimulated by nutrients. Preliminary studies have revealed that the commensal bacterium Enterococcus faecalis V583 induces the prophages when growing in the mouse intestine. In vitro, prophage induction depends on elevated amino acid concentrations; however, the exact mechanisms underlying nutrient-mediated induction of prophages are unknown. Further, in vivo studies indicate that the release of lytic phage particles allows E. faecalis to compete with genetically related enterococci vying for similar intestinal resources. Together, these initial findings indicae that phages can impact the dynamics of bacterial colonization in the mammalian intestinal ecosystem and have established E. faecalis prophages as model intestinal phages for the study of phage-host interactions. The long-term goal of this research is to understand how intestinal bacteriophages impact human physiology and health. The specific research proposed under this K01 award mechanism will advance this goal by defining the mechanisms that elicit phage production in the intestine, by determining how bacteriophage impact host immunity, and by exploring how phage predation impacts bacterial interactions with the host. These studies will provide novel insights into how intestinal phages influence host health and physiology, and will set the stage for future exploration of phage as therapeutic tools for manipulating the microbiota to improve health.

描述（由申请人提供）：哺乳动物肠道是密集细菌群落的家园，这些细菌对宿主健康至关重要。这种细菌种群的改变会导致肠道不适，甚至在某些情况下导致炎症性疾病。除了细菌之外，肠道中也大量存在病毒。真核病毒和原核病毒都构成肠道“病毒组”，但感染细菌的病毒（称为噬菌体）占主导地位。大多数肠道噬菌体以溶原性噬菌体形式存在，稳定整合到细菌染色体中。当细菌细胞受到应激或受到营养物刺激时，原噬菌体通常会经历裂解诱导，产生感染性噬菌体颗粒。初步研究表明，共生细菌粪肠球菌 V583 在小鼠肠道中生长时会诱导产生噬菌体。在体外，前噬菌体的诱导取决于氨基酸浓度的升高；然而，营养介导的前噬菌体诱导的确切机制尚不清楚。此外，体内研究表明，裂解噬菌体颗粒的释放使粪肠球菌能够与遗传相关的肠球菌竞争相似的肠道资源。总之，这些初步发现表明噬菌体可以影响哺乳动物肠道生态系统中细菌定植的动态，并已建立粪肠球菌原噬菌体作为研究噬菌体-宿主相互作用的模型肠道噬菌体。这项研究的长期目标是了解肠道噬菌体如何影响人体生理和健康。 K01 奖励机制下提出的具体研究将通过定义在肠道中引发噬菌体产生的机制、确定噬菌体如何影响宿主免疫以及探索噬菌体捕食如何影响细菌与宿主的相互作用来推进这一目标。这些研究将为肠道噬菌体如何影响宿主健康和生理学提供新的见解，并为未来探索噬菌体作为操纵微生物群以改善健康的治疗工具奠定基础。