Accelerated evolution of antibiotic resistance in a bacterial swarm

细菌群中抗生素耐药性的加速进化

• 批准号: 10377986
• 负责人: Rasika M Harshey
• 金额: $ 19.81万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-25 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10377986
• 关键词: Address; Affect; Altruism; Antibiotic Resistance; Antibiotics; Bacteria; Bar Codes; Base Excision Repairs; Binding; Case Study; Cells; Cessation of life; DNA Repair Pathway; Data; Diagnosis; Down-Regulation; Drug Efflux; Environment; Escherichia coli; Evolution; Exhibits; Exposure to; Frequencies; Future; Gene Expression; Genes; Genetic; Genetic Transcription; Growth; Incubators; Investigation; Lead; Libraries; Link; Metabolic; Microbial Biofilms; Mutation; Pathway Analysis; Pathway interactions; Pharmacotherapy; Physiology; Process; Proteins; Regulation; Reporter; Resistance; Stress; Surface; Testing; Time; Up-Regulation; antibiotic tolerance; base; commune; cost; efflux pump; experimental study; fitness; gene function; genetic resistance; non-genetic; programs; repaired; transcriptome sequencing

Accelerated evolution of antibiotic resistance in a bacterial swarm Many bacterial species band together as a dense collective and migrate over surfaces in a process called swarming. Swarms exhibit high tolerance to a broad class of antibiotics, reminiscent of the tolerance seen in biofilms and other settings. Unlike the latter environments however, where slower bacterial growth rates and lower metabolic activity are implicated in the higher tolerance to drug treatment, bacterial swarms are metabolically highly active and grow robustly. Thus, the tolerance exhibited by swarms is apparently distinct from the other reported cases of this phenomenon. We made significant recent progress in understanding tolerance in E. coli swarms when we discovered that swarms are intrinsically programmed to upregulate expression of multiple drug efflux pumps and of ROS pathways that protect against antibiotic stress. At the same time, swarms also downregulate expression of genes involved in mismatch and base-excision DNA repair pathways. Consistent with this observation, preliminary data show that swarms have higher mutation rates and are more proficient at evolving genetic resistance to antibiotics compared to their planktonic counterparts. The fitness cost associated with higher mutation rates apparently outweighs the advantage of evolvability to genetic resistance. We propose to investigate how the intrinsic program for upregulating Efflux pathways unfolds. We also propose to investigate the link between upregulation of Efflux and downregulation of DNA repair pathways. Interfering with evolvability to resistance, hence tolerance, is perhaps as important as combating resistance itself. Investigation of the underlying tolerance mechanisms may in the future, lead to genetic or physiology-based markers for diagnosis, treatment, and eradication.

细菌群中抗生素耐药性的加速进化