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

描述（由申请人提供）：哺乳动物肠道是宿主健康不可或缺的密集细菌群落的家园。这种细菌群的改变可引起肠道不适，甚至在某些情况下引起炎症性疾病。除了细菌外，肠道中也有大量的病毒。真核病毒和原核病毒都构成了肠道“病毒组”，然而，感染细菌的病毒，称为噬菌体（Bacteriophage，简称噬菌体），占主导地位。大多数肠道细菌以稳定整合到细菌染色体中的溶原性原噬菌体的形式存在。当细菌细胞受到应激或当它们受到营养物刺激时，益生菌通常经历裂解诱导以产生感染性噬菌体颗粒。初步研究表明，肠道细菌粪肠球菌V583在小鼠肠道中生长时诱导原噬菌体。在体外，原噬菌体诱导依赖于升高的氨基酸浓度;然而，营养介导的原噬菌体诱导的确切机制尚不清楚。此外，体内研究表明，裂解性噬菌体颗粒的释放允许E.粪球菌与遗传相关的肠球菌竞争类似的肠道资源。总之，这些初步的发现表明，大肠杆菌可以影响哺乳动物肠道生态系统中细菌定植的动力学，并建立了大肠杆菌。粪球菌前噬菌体作为研究噬菌体-宿主相互作用的模型肠道菌群。这项研究的长期目标是了解肠道噬菌体如何影响人类的生理和健康。根据K 01奖励机制提出的具体研究将通过定义引发肠道中噬菌体产生的机制，确定噬菌体如何影响宿主免疫力，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。这些研究将为肠道菌群如何影响宿主健康和生理提供新的见解，并将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。

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.