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

基本信息

批准号：
8920567
负责人：
Breck A Duerkop
金额：
$ 10.07万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/8920567
关键词：
Amino Acids Antiviral Agents Bacteria Bacterial Chromosomes Bacteriophages Biological Models Biology Cells Cellular Stress Communities Coupled Cytolysis Disease Distress Ecology Ecosystem Enterococcus Enterococcus faecalis Epithelial Epithelial Cells Foundations Future Genes Genetic Goals Health Home environment Human Immune Immune response Immune system Immunity In Vitro Infection Inflammatory Intestines Invaded Lytic Measures Mediating Mentored Research Scientist Development Award Microbe Modeling Mus Mutagenesis Natural Immunity Nutrient Pathway interactions Physiology Plaque Assay Population Predatory Behavior Production Prophage Inductions Prophages Reporter Research Resources Role Shapes Staging Surface Systemic infection Testing Therapeutic Tissues Viral Virus Work base combat commensal microbes detection of nutrient gut microbiota improved in vivo insight microbial monolayer mouse model mutant novel particle tool virome

项目摘要

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）：哺乳动物肠道是一个密集的细菌群落的家园，它们是宿主健康不可或缺的。这种细菌种群CA的改变会导致肠道困扰，甚至在某些情况下炎症性疾病。除细菌外，肠道中还丰富了病毒。真核和原核病毒构成了肠道“病毒瘤”，但是，感染细菌（称为噬菌体（噬菌体））的病毒占主导地位。大多数肠道噬菌体作为溶酶体预言存在，这些预言稳定地整合到细菌染色体中。当细菌细胞受到压力或营养刺激时，预言通常会经历裂解诱导，以产生传染性的噬菌体颗粒。初步研究表明，共生细菌肠球菌V583在小鼠肠中生长时会诱导预言。在体外，预言诱导取决于氨基酸浓度升高。但是，尚不清楚营养介导的预言诱导的基本机制。此外，体内研究表明，裂解噬菌体颗粒的释放允许粪肠球菌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生态系统中细菌定植的动力学，并已建立了粪肠球菌的预言作为模型肠噬菌体，用于研究噬菌体 - 宿主相互作用。这项研究的长期目标是了解肠噬菌体如何影响人类的生理和健康。根据本K01奖励机制提出的具体研究将通过确定引起肠道噬菌体产生的机制，确定噬菌体如何影响宿主的免疫，并探索噬菌体捕食如何影响细菌与宿主的相互作用，从而推进这一目标。这些研究将为肠道噬菌体如何影响宿主的健康和生理学提供新的见解，并为将来探索噬菌体作为治疗微生物群以改善健康的治疗工具奠定了基础。