Defining the antibiotic intrinsic resistome of Acinetobacter baumannii

鲍曼不动杆菌抗生素固有耐药组的定义

• 批准号: 10220708
• 负责人: Colin Manoil
• 金额: $ 27.21万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220708
• 关键词: Acinetobacter baumannii; Alleles; Antibiotic Resistance; Antibiotics; Bacteria; Biochemical; Biological Assay; Cell Membrane Permeability; Cell physiology; Clinical; Colistin; DNA; DNA-Directed RNA Polymerase; Enzymes; Essential Genes; Exhibits; Foundations; Gene Mutation; Gene Order; Goals; Growth; In Vitro; Infection; Membrane; Meropenem; Methods; Mutation; Phenotype; Procedures; Residual state; Resistance; Testing; Tobramycin; Work; biological adaptation to stress; capsule; carbapenemase; clinically relevant; colistin resistance; efflux pump; experimental study; genome-wide; loss of function; mutant; new technology; novel; null mutation; pathogen; resistance gene; resistance mechanism; trait

The project aims to define the functional basis of Acinetobacter baumannii intrinsic resistance to three clinically-relevant antibiotics (meropenem, colistin, and tobramycin) at a comprehensive scale. The work will identify resistance functions at genome-scale using transposon mutant sequencing, and will validate results through single mutant testing. The study will employ new technology that makes it possible to include mutants inactivating essential genes, which is usually missing from such studies. Top, validated mutants exhibiting increased sensitivity to one or more of the antibiotics will be further evaluated for whether they act through established or novel resistance mechanisms.

该项目旨在明确鲍曼不动杆菌内在的功能基础 对三种临床相关抗生素（美罗培南、粘菌素和妥布霉素）的耐药性 综合规模。这项工作将在基因组规模上识别抗性功能 使用转座子突变体测序，并将通过单突变体验证结果 测试。该研究将采用新技术，使突变体纳入成为可能 使必需基因失活，而此类研究通常缺少这种基因。顶部，已验证 对一种或多种抗生素表现出更高敏感性的突变体将进一步 评估它们是否通过已建立的或新的抵抗机制起作用。

项目成果

Genetic Dissection of Antibiotic Adjuvant Activity.

• DOI: 10.1128/mbio.03084-21
• 发表时间: 2022-02-22
• 期刊: mBio
• 影响因子: 6.4
• 作者: Bailey J;Gallagher L;Barker WT;Hubble VB;Gasper J;Melander C;Manoil C
• 通讯作者: Manoil C