Characterizing novel Beta-lactamases from metagenomic samples: insights into the evolution of antimicrobial resistance from the environment towards human-associated pathogens

从宏基因组样本中表征新型 β-内酰胺酶：深入了解从环境到人类相关病原体的抗菌药物耐药性的演变

• 批准号: 10708776
• 负责人: Pablo Power
• 金额: $ 12.68万
• 依托单位: UBATEC S.A.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708776
• 关键词: Alaska; Alaskan; Antarctica; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Attention; Bacteria; Biochemical; Biological; Biological Assay; Carbapenems; Classification; Clinic; Clinical; Cloning; Collection; Crystallization; Early Diagnosis; Environment; Enzymes; Evolution; Exhibits; Exposure to; Frequencies; Fright; Genes; Genetic; Health; Hospitals; Human; Kinetics; Lactamase; Mediating; Metagenomics; Methods; Mission; Molecular; Mutagenesis; Mutation; Names; National Institute of Allergy and Infectious Disease; Natural Selections; Nature; Phenotype; Physicians; Process; Production; Proteins; Public Health; Research; Resistance; Risk; Role; Route; Sampling; Site-Directed Mutagenesis; Soil; Source; Spectrophotometry; Structure; System; Techniques; United States National Institutes of Health; Variant; X ray diffraction analysis; beta-Lactam Resistance; beta-Lactamase; beta-Lactams; carbapenem resistance; carbapenemase; enzyme pathway; insight; member; metagenome; microorganism; novel; pathogen; pathogenic bacteria; recruit; remote location; repository; resistance mechanism; screening; soil sampling; trend

PROJECT SUMMARY β-Lactamases are the most widespread resistance mechanism to β-lactam antibiotics. Of particular concern are a group of β-lactamases known as carbapenemases, named for their ability to destroy our newest β-lactam antibiotics, the carbapenems. The rise of carbapenem resistance is a recent global trend that has resulted in pan-national fear. An interesting approach to understand carbapenem resistance and how it evolves is through quantitative analysis of non-pathogenic microorganisms found in the environment. Analysis of these microorganisms offers the intriguing possibility of predicting how antibiotic resistance may evolve and provides clinicians with an “early warning” system for the advent of novel resistance mechanisms in pathogenic bacteria. Previous research has shown that the soil is an excellent repository for many β-lactamases, especially carbapenemases. The main part of the project will be the study of a collection of metagenome-origin β-lactamases isolated from Alaskan soil, named LRA (for “β-lactam resistance from Alaska”). This metagenomic approach will be expanded and applied to the analysis of soil samples from Antarctica to identify β-lactamase-mediated resistance in different isolated regions. Identified environmental β-lactamases will be characterized using a multi-pronged approach involving phenotypic, molecular, biochemical and structural techniques. Specifically, results from this comprehensive analysis will allow us to assess the evolutionary routes of β-lactamases found among clinical pathogens that plague human health today, and to evaluate novel niches of potentially unexplored genes that could be recruited by these pathogens.

项目总结