Mechanisms of antibiotic resistance development in bacterial pathogens

细菌病原体抗生素耐药性发展机制

基本信息

批准号：
9761963
负责人：
Houra Merrikh
金额：
$ 39.25万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-13 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9761963
关键词：
Alkylation Antibiotic Resistance Antibiotic Therapy Antibiotics Antimicrobial Resistance Area Automobile Driving Bacillus subtilis Bacteria Bacterial Antibiotic Resistance Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Clinical Conflict (Psychology)Cytosine DNA DNA biosynthesis DNA lesion DNA-Directed RNA Polymerase Data Deamination Development Dose Drops Drug Targeting Engineering Event Evolution Future Genes Genetic Transcription Genome Goals Heritability Infection Investigation Kinetics Lead Lesion Measures Mediating Messenger RNA Modeling Molecular Mutagenesis Mutation Mycobacterium smegmatis Mycobacterium tuberculosis Organism Oxidative Stress Pharmaceutical Preparations Phenotype Positioning Attribute Predisposition Prevalence Prevention strategy Process Proteins Pseudomonas aeruginosa Reporter Research Resistance Resistance development Role Salmonella typhimurium Severities Staphylococcus aureus Technical Expertise Techniques Testing Time Transcription-Coupled Repair Work base drug resistant pathogen environmental change epigenetic variation experience experimental study genome-wide analysis global health human pathogen infectious disease treatment microbial microorganism next generation sequencing novel strategies novel therapeutics pathogen pathogenic bacteria programs public health relevance repair enzyme resistance gene

项目摘要

Project Summary: Microorganisms evolve quickly under selective conditions and can rapidly adapt to environmental changes. We recently discovered that transcription-coupled repair (TCR), and, encounters between the DNA replication and transcription machineries (conflicts) increase mutagenesis significantly in specific genes. We subsequently identified the factors required for these mutagenesis mechanisms. We now find that these factors promote antibiotic resistance development in bacteria. Here, using various experimental techniques, we plan to investigate the impact of TCR and conflicts on evolution of antibiotic resistance in important human pathogens, as well as deepen our understanding of the underlying mechanisms promoting this adaptive process. We are putting forth a research program with a novel approach to circumvent a global health crisis: a study tailored towards characterization of potential drug targets that promote evolution of antibiotic resistance in bacterial pathogens.

项目摘要：微生物在选择性条件下迅速发展，并且可以迅速适应环境更改。我们最近发现转录耦合修复（TCR），并在DNA之间遇到在特定基因中，复制和转录机器（冲突）显着增加了诱变。我们随后确定了这些诱变机制所需的因素。我们现在发现这些因素促进细菌中的抗生素耐药性发展。在这里，使用各种实验技术，我们计划研究TCR和冲突对重要人类病原体中抗生素抗性进化的影响，以及加深我们对促进这种适应过程的基本机制的理解。我们是提出一种研究计划，采用一种新颖的方法来规避全球健康危机：一项量身定制的研究朝着促进细菌中抗生素耐药性进化的潜在药物靶标表征病原体。