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环丙沙星对铜绿假单胞菌的耐药机制:一个老问题的新方法

发布者:抗性基因网 时间:2019-01-07 浏览量:2041

摘要

抗生素环丙沙星广泛用于治疗由机会性病原体铜绿假单胞菌引起的各种感染。由于其广泛使用,环丙沙星抗性铜绿假单胞菌分离物的比例正在迅速增加。通过获得编码环丙沙星的靶蛋白和外排泵的调节剂的基因中的突变,可以产生环丙沙星抗性,这导致这些泵的过表达。但是,对环丙沙星耐药性基础的了解尚未完成。使用高通量筛选和实验进化以及全基因组测序和蛋白质分析的最新进展增强了我们对环丙沙星抗性所涉及的遗传和生化机制的理解。更好地了解环丙沙星耐药机制可能有助于开发有效对抗铜绿假单胞菌的新的或改进的治疗方案。在这篇综述中,我们讨论了目前对环丙沙星耐药机制的理解,并总结了铜绿假单胞菌环丙沙星耐药的遗传基础,在目前和将来使用这种抗生素的背景下。


The antibiotic ciprofloxacin is used extensively to treat a wide range of infections caused by the opportunistic pathogen Pseudomonas aeruginosa. Due to its extensive use, the proportion of ciprofloxacin-resistant P. aeruginosa isolates is rapidly increasing. Ciprofloxacin resistance can arise through the acquisition of mutations in genes encoding the target proteins of ciprofloxacin and regulators of efflux pumps, which leads to overexpression of these pumps. However, understanding of the basis of ciprofloxacin resistance is not yet complete. Recent advances using high-throughput screens and experimental evolution combined with whole-genome sequencing and protein analysis are enhancing our understanding of the genetic and biochemical mechanisms involved in ciprofloxacin resistance. Better insights into the mechanisms of ciprofloxacin resistance may facilitate the development of new or improved therapeutic regimes effective against P. aeruginosa. In this review we discuss the current understanding of the mechanisms of ciprofloxacin resistance and summarize the genetic basis of ciprofloxacin resistance in P. aeruginosa, in the context of current and future use of this antibiotic.


https://www.ncbi.nlm.nih.gov/pubmed/30605076