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Elucidating ecological mechanisms for propagation of antibiotic resistance genes via massively parallelized single-cell sequencing

通过大规模并行单细胞测序阐明抗生素抗性基因传播的生态机制

基本信息

批准号：
10362535
负责人：
Ophelia Venturelli
金额：
$ 23.33万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-02 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10362535
关键词：
Address Antibiotic Resistance Antibiotic Therapy Antibiotics Automobile Driving Bacteria Bacterial Antibiotic Resistance Bar Codes Base Sequence Biological Assay Cells Clinic Communicable Diseases Communities Complex Cytolysis DNA purification Data Detection Ecosystem Encapsulated Exhibits Frequencies Gel Generations Genes Genetic Germ-Free Horizontal Gene Transfer Human Immunocompromised Host Infection Internet Knowledge Lead Mediating Metagenomics Methods Mobile Genetic Elements Modeling Mus Population Process Public Health Sampling Series Shotguns Stress Taxonomy Technology Time antibiotic design bacterial resistance clinically relevant computational pipelines cost data analysis pipeline design drug resistant pathogen emerging antibiotic resistance experimental study fecal microbiome genome sequencing genomic locus global health gut microbiome gut microbiota human microbiota insight member microbial microbial community microbial host microbiome microfluidic technology new technology next generation sequencing pathogen pressure resistance gene resistant strain response single cell analysis single cell sequencing targeted sequencing therapy design transmission process treatment strategy whole genome

项目摘要

PROJECT SUMMARY The accelerating emergence of antibiotics resistant bacteria has become a global health crisis, costing tens of thousands of lives and hundreds of billions of dollars every year. Horizontal transfer of antibiotics resistance genes (ARGs) is a key mechanism driving the emergence of antibiotic resistant strains, but the ecological processes impacting the transmission of these genes through microbial communities are largely unknown. To address this knowledge gap, we propose to develop an ultrahigh-throughput single cell sequencing technology to identify the associations between ARGs and microbial taxa. This method will be used to decipher the time- dependent horizontal gene transfer networks underlying ARG spread in a human gut microbiome in response to clinically relevant antibiotics. The new technology will enable single cell analysis of microbial communities at an unprecedented scale. Deciphering the horizontal gene transfer networks responsible for ARG dissemination will deepen our understanding of the ecological interactions involved in the emergence of antibiotic resistant bacteria and inform the design of interventions to substantially reduce ARG propagation. A detailed understanding of the environmental and ecological factors influencing horizontal gene transfer is critical to combating infectious diseases.

项目摘要抗生素耐药性细菌的加速出现已成为全球健康危机，成千上万的生命和数千亿美元的损失抗生素耐药性的水平转移基因（ARG）是驱动抗生素耐药菌株出现的关键机制，但生态学影响这些基因通过微生物群落传递的过程在很大程度上是未知的。到为了解决这一知识缺口，我们建议开发一种超高通量的单细胞测序技术，以确定ARG和微生物类群之间的关联。这个方法将被用来破译时间- ARG在人类肠道微生物组中传播的依赖性水平基因转移网络临床相关抗生素。这项新技术将使微生物群落的单细胞分析成为可能，前所未有的规模。破译负责ARG传播的水平基因转移网络将加深我们对抗生素耐药性细菌出现所涉及的生态相互作用的理解并告知干预措施的设计，以大大减少ARG传播。详细了解影响水平基因转移的环境和生态因素对防治传染病至关重要。疾病