Antibiotic Hypersusceptibility Mutations in Bacteria

细菌中的抗生素过敏突变

• 批准号: 6621233
• 负责人: ALEX A NEYFAKH
• 金额: $ 34.42万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-15 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621233
• 关键词: Escherichia coli; Neisseriaceae; ampicillin; antibacterial agents; antibiotics; bacterial genetics; bacterial proteins; beta lactam antibiotic; chloramphenicol; erythromycin; gene mutation; gram negative bacteria; macrolide antibiotics; microorganism culture; pharmacology; tetracyclines

DESCRIPTION (Adapted from the Applicant's Abstract): The escalating problem of bacterial resistance to antibiotics calls for radical changes in the existing antibacterial therapies. One of the most promising approaches is the use of antibiotic potentiators, compounds that make bacterial cells hypersusceptible to antibiotics. The goal of the project is to identify multiple novel molecular targets for potentiators. This will be accomplished by isolating antibiotic hypersusceptibility mutations of Gram-negative bacteria, Acinetobacter and/or Escherichia coli. These mutations will specify bacterial proteins whose inhibition is likely to potentiate antimicrobial action of antibiotics. Antibiotic hypersusceptibility is a very difficult phenotype to select, and only few such mutations are known. We have designed and tested a novel genetic strategy for selection of hypersusceptibility mutations, termed SDR. Application of this strategy will identify multiple mutations increasing bacterial susceptibility to beta-lactams (ampicillin, ceftazidime, imipenem), translational inhibitors (erythromycin, linezolid, tetracycline, and chloramphenicol) and fluoroquinolone antibiotics (ciprofloxacin). The molecular mechanisms underlying the effects of the most interesting of these mutations will be analyzed. In addition to identifying promising targets for potentiators, the project will help unravel new aspects of the mechanism of action of antibiotics and new features of bacterial physiology.

描述（改编自申请人的摘要）： 细菌对抗生素的耐药性需要在现有的 抗菌疗法。最有前途的方法之一是使用 抗生素增强剂，使细菌细胞过度敏感的化合物 抗生素。该项目的目的是识别多个新型分子 实力剂的目标。这将通过隔离抗生素来完成 革兰氏阴性细菌，杆菌和/或的超敏度突变 大肠杆菌。这些突变将指定细菌蛋白 抑制可能会增强抗生素的抗菌作用。 抗生素过度敏感性是很难选择的表型，并且 只有很少的这种突变是已知的。我们设计并测试了一种新型遗传 选择超敏度突变的策略，称为SDR。 该策略的应用将识别多个突变的增加 细菌对β-内酰胺的敏感性（氨苄西林，头孢氮蛋白酶，imipenem）， 翻译抑制剂（红霉素，linezolid，四环素和 氯霉素）和氟喹诺酮抗生素（环丙沙星）。分子 这些突变中最有趣的效果的基础机制 将进行分析。除了确定有希望的目标 该项目将有助于揭开新机制的新方面 抗生素的作用和细菌生理学的新特征。