Host and symbiont determinants of colonization by a co-evolved gut community

共同进化的肠道群落定植的宿主和共生体决定因素

• 批准号: 8603715
• 负责人: Nancy A. Moran
• 金额: $ 34.76万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-02 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603715
• 关键词: Address; Affect; Animals; Apidae; Apis; Bacteria; Bacterial Genes; Bees; Biology; Characteristics; Communities; Complex; Development; Drosophila genus; Enabling Factors; Environment; Food; Fostering; Foundations; Genes; Genetic; Genome; Genotype; Health; High-Throughput Nucleotide Sequencing; Hindgut; Honey; Human; Human Development; Individual; Insecta; Integration Host Factors; Laboratories; Lead; Mammals; Mediating; Metabolic; Methods; Microbe; Modeling; Monitor; Mutagenesis; Mutation; Nomenclature; Pathway interactions; Process; Protocols documentation; Publishing; RNA Interference; Resources; Specificity; System; Work; axenic culture; base; disease characteristic; genome sequencing; genome-wide; gut microbiota; ileum; member; microbial community; mutant; pathogenic bacteria; public health relevance; response; screening; tool; transcriptome sequencing

Host and symbiont determinants of colonization by a co-evolved gut community Project Summary Host-specific gut bacteria are central to the biology and health of animals, but elucidating the processes that govern normal and atypical assembly of gut communities is challenging. Most gut communities, and specifically those of humans, are dauntingly complex; whereas others, such as that of Drosophila, have variable compositions dominated by opportunistic bacterial species from other environments. In the honey bee (Apis mellifera), the ileum region of the hindgut contains a dense but simple community dominated by only three specialized bacterial species that comprise >95% of bacteria despite the continual entry of diverse environmental microbes present in food. These three species are found only in bee guts, and distinct but related strains are found in related bee species. Our pilot work established axenic culture conditions, official nomenclature, and reference strains for all bee gut community members, transposon-based mutagenesis methods, protocols for controlling colonization with specific isolates or mutants, and methods for quantitative description of community composition. Furthermore, the host is amenable to genetic studies: sequenced genome and associated resources are available for the honey bee, and RNAi methods have been established. Building on these foundations, we will use the honey bee ileum as a model gut community to determine the specific bacterial and host factors that underlie the establishment of a persistent gut community characteristic of a host species. We will use expression analyses and genome-wide mutagenesis and mutant screening based on high-throughput sequencing to identify symbiont genes affecting colonization of the bee ileum and to elucidate the effects of host genes and pathways on colonization. We will examine how a focal pioneer symbiont influences the assembly and subsequent composition of the gut community. This will be achieved by monitoring succession in experimental gut communities and by identifying symbiont genes that affect colonization by other bacterial species and strains, including both the symbionts normally present in the community and the opportunistic or pathogenic bacteria that are typically excluded. These results will reveal host and symbiont-based processes that govern development of a normal, host- specific gut microbiota and will illuminate how and why gut communities sometimes develop abnormally, to the detriment of host health. !

共同进化的肠道群落定殖的宿主和共生体决定因素 项目摘要 宿主特异性肠道细菌对动物的生物学和健康至关重要，但阐明宿主特异性肠道细菌对动物的生物学和健康至关重要。 控制肠道群落的正常和非典型组装的过程具有挑战性。最有胆量 社区，特别是人类的社区，是令人生畏的复杂;而其他社区，如 果蝇的，具有可变的组成，由机会细菌物种占主导地位， 其他环境。在蜜蜂（Apis mellifera）中，后肠的回肠区域含有一个 密集而简单的群落，只有三种专门的细菌物种， 尽管食物中存在的各种环境微生物不断进入，但细菌仍占95%以上。 这三个物种只在蜜蜂的内脏中发现，不同但相关的菌株在相关的 蜜蜂种类我们的试点工作建立了无菌培养条件，官方命名， 所有蜜蜂肠道群落成员的参考菌株，基于转座子的诱变方法， 控制特定分离物或突变体定殖的方案，以及定量测定 社区组成的描述。此外，宿主适合遗传研究： 已测序的基因组和相关资源可用于蜜蜂， 已经建立。在这些基础上，我们将使用蜜蜂回肠作为模型 肠道菌群，以确定建立的特定细菌和宿主因素 一种宿主物种特有的持久性肠道群落。我们将使用表情分析 以及基于高通量测序的全基因组诱变和突变体筛选， 鉴定影响蜜蜂回肠定殖的共生体基因，并阐明宿主 基因和途径的影响。我们将研究一个焦点先锋共生体如何影响 组装和随后的肠道群落组成。这将通过监测 实验肠道群落的演替，并通过识别影响 其他细菌种属和菌株的定植，包括通常存在的共生体 以及通常被排除在外的机会性或致病性细菌。这些 结果将揭示主机和共生体为基础的过程，支配发展的正常，主机- 特定的肠道微生物群，并将阐明如何以及为什么肠道社区有时发展 不正常地，损害宿主的健康。 !