Ciprofloxacin resistance and compensatory Mutations.

环丙沙星耐药性和补偿性突变。

• 批准号: 6724821
• 负责人: JULIAN P. ADAMS
• 金额: $ 22.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6724821
• 关键词: Bacillus subtilis; Escherichia coli; antibacterial agents; bacterial genetics; biochemical evolution; drug resistance; gene mutation; microorganism culture; novobiocin; nucleic acid sequence; polymerase chain reaction

DESCRIPTION (provided by applicant): The evolution of antibiotic resistance in human pathogenic microorganisms is increasingly becoming a serious public health problem. A number of measures have been proposed to combat the spread of antibiotic resistance with varying success, including controls of the use of antibiotics, the use of vaccines and improvement of hospital hygiene. However, the ultimate success of such measures is questionable, due to evolutionary changes in the resistant sector of the microorganism populations. Many (but not all) mutations to antibiotic resistance are deleterious, and therefore may be selected against in the absence of the antibiotic. However, under prolonged exposure to antibiotics, compensatory mutations can and do occur and be selected, which reduce the cost associated with antibiotic resistance. Such evolutionary changes will contribute to the prevalence to antibiotic resistant pathogens, and render some antibiotics ineffective. Such a scenario will be particularly disastrous during an anthrax epidemic in this country, for which ciprofloxacin will be the primary antibiotic of choice. The principal focus of this project will be to characterize and identify compensatory mutations, which reduce the cost of ciprofloxacin resistance in B. subtilis, a close relative of B. anthracis. The study will also be extended to include E. coli and two other antibiotics, novobiocin and ceftazidime. Knowledge of the biochemical and physiological basis of compensatory mutations may allow the design of strategies to reduce or counteract their role in increasing the prevalence of antibiotic resistant mutations.

描述（由申请人提供）： 人类病原微生物抗生素耐药性的演变日益成为一个严重的公共卫生问题。已提出了一些措施来遏制抗生素耐药性的蔓延，取得了不同程度的成功，包括控制抗生素的使用、疫苗的使用和改善医院卫生。然而，这些措施的最终成功是值得怀疑的，由于在微生物种群的耐药部门的进化变化。许多（但不是所有）抗生素耐药性突变都是有害的，因此可以在不使用抗生素的情况下进行选择。然而，在长期暴露于抗生素的情况下，补偿性突变可以并且确实发生并被选择，这降低了与抗生素耐药性相关的成本。这种进化变化将导致抗生素耐药病原体的流行，并使一些抗生素无效。在这个国家炭疽病流行期间，这种情况将是特别灾难性的，环丙沙星将是首选的主要抗生素。该项目的主要重点将是表征和鉴定补偿突变，这将降低B中环丙沙星耐药性的成本。枯草芽孢杆菌（B. subtilis）是B的近亲。炭疽病 这项研究还将扩展到包括E。大肠杆菌和其他两种抗生素新生霉素和头孢他啶。补偿突变的生化和生理基础的知识，可以允许设计的策略，以减少或抵消其作用，增加抗生素耐药突变的患病率。