Circadian Regulation of Antibiotic Resistance in the Microbiome

微生物组抗生素耐药性的昼夜节律调节

基本信息

批准号：
10625329
负责人：
Alexander Crofts
金额：
$ 2.4万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10625329
关键词：
Address Antibiotic Resistance Automobile Driving Bacteria Bacterial Antibiotic Resistance Bacterial Genes Bacterial Infections Behavior Control Characteristics Circadian Dysregulation Circadian Rhythms Data Diurnal Rhythm Event Evolution Feeding behaviors Gene Expression Gene Expression Regulation Gene Transfer Genetic Conjugation Genetic Transcription Goals Health Horizontal Gene Transfer Hour Human Integration Host Factors Intestines Investigation Light Microbe Modeling Mus Outcome Pattern Periodicity Physiology Plasmids Process Regulation Resistance Resistance development Structure System Testing Time Transcript Work antibiotic resistant infections circadian circadian pacemaker circadian regulation clinically significant global health gut bacteria gut microbes gut microbiome gut microbiota in vivo insight member metatranscriptomics microbiome microbiome composition microbiota mouse model multiple omics novel resistance gene resistance mechanism

项目摘要

Project Summary Humans must regulate a symbiotic relationship with almost 100 trillion intestinal bacteria which readily harbor antibiotic resistance genes and the mechanisms that spread them. Despite the relentless rise of antibiotic resistant infections little is known about the host factors that regulate antibiotic resistance development in vivo. Preliminary investigations revealed that the mammalian circadian clock may be such a factor. Prior in vivo studies have demonstrated that the circadian clock drives daily rhythms in microbiome composition which are synchronized to the day-night cycle. However, gene expression in the microbiome at circadian time scales is largely unexplored. To this end, a comprehensive study of the mouse microbiome was performed across the day-night light cycle. These data revealed that beyond daily rhythms of microbe abundances, extensive transcriptional rhythms occur in the microbiome across the day-night light cycle. Indeed, antibiotic resistance and horizontal gene transfer systems showed some of the most significant transcriptional rhythms in the microbiome, reaching peak expression within a 4-hour window each day. These preliminary data demonstrated that transcription in the microbiome is temporally structured in vivo. These diurnal (daily) rhythms are characteristic of regulation by the host’s circadian clock. Therefore, this proposal seeks to understand mechanisms driving diurnal bacterial transcription in the microbiome by examining the in vivo regulation of horizontal gene transfer and the impact of the host circadian clock on the spread of antibiotic resistance. Taken together, this work proposes the circadian clock synchronizes transcription in the microbiome to the day-night cycle, potentially revealing a mammalian regulator of antibiotic resistance development.

项目摘要人类必须与近100万亿肠Bactteria建立共生关系抗生素抗性基因及其传播的机制。抗药性感染对宿主知之甚少。初步研究表明，哺乳动物昼夜节律可能是一个事先的体内研究。已经证明，圆形时钟驱动微生物组组成的每日节奏然而，与昼夜的Chycle同步。在很大程度上没有探索。昼夜light Chycle。转录节奏在整天的光周期中发生在微生物组中水平基因转移系统显示出一些最显着的转录节律微生物组，每天在4小时内表达峰值。微生物组中的转录是在体内结构的。因此，主持人的昼夜节律的特征。通过检查体内调节的机制来驱动微生物组的昼夜体内调节水平基因转移和宿主昼夜节律对抗生素耐药性的影响。这项工作共同提出了昼夜节律时钟将微生物组中的转录同步到夜晚循环，有可能揭示出抗生素耐药性发展的mamalian调节剂。