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Potential genes associated with survival of Acinetobacter baumannii under ciprofloxacin stress
Microbes and Infection ( IF 2.6 ) Pub Date : 2021-11-29 , DOI: 10.1016/j.micinf.2021.104844
Shruti Kashyap 1 , Prince Sharma 2 , Neena Capalash 1
Affiliation  

Acinetobacter baumannii is an opportunistic pathogen that has acquired resistance to all available drugs. The rise in multi-drug resistance in A. baumannii has been exacerbated by its ability to tolerate antibiotics due to the persister cells, which are phenotypic variants of normal cells that can survive various stress conditions, resulting in chronicity of infection. In the present study we observed that A. baumannii formed persister cells against lethal concentration of ciprofloxacin in exponential phase. The transcriptome of A. baumannii was analyzed after exposure to high concentration of ciprofloxacin (50X MIC) to determine the possible mechanisms of survival. Transcriptome analysis showed differential expression of 146 genes, of which 101 were up-regulated and 45 were down-regulated under ciprofloxacin stress. Differentially expressed genes that might be important for persistence against ciprofloxacin were involved in DNA repair, phenylacetic acid degradation, leucine catabolism, HicAB toxin-antitoxin system and ROS response (iron-sulfur clusters, hemerythrin-like metal binding and Kdp). recA, umuD and ddrR genes involved in SOS response were also up-regulated. Knockout of umuD showed significant decrease in persister cells formation while they were completely eradicated in recA mutant strain. The differentially expressed genes highlighted in the study merit further investigation as therapeutic targets for effective control of A. baumannii infections.



中文翻译:

与环丙沙星胁迫下鲍曼不动杆菌存活相关的潜在基因

鲍曼不动杆菌是一种机会性病原体,已对所有可用药物产生耐药性。由于持久性细胞是正常细胞的表型变异,可以在各种压力条件下存活,导致感染的慢性化,从而加剧了鲍曼不动杆菌的多药耐药性。在本研究中,我们观察到鲍曼不动杆菌在指数期形成针对致死浓度的环丙沙星的持久细胞。A. baumannii的转录组在暴露于高浓度环丙沙星 (50X MIC) 后进行分析以确定可能的存活机制。转录组分析显示146个基因的差异表达,其中101个上调,45个在环丙沙星胁迫下下调。可能对环丙沙星的持久性很重要的差异表达基因参与 DNA 修复、苯乙酸降解、亮氨酸分解代谢、HicAB 毒素-抗毒素系统和 ROS 反应(铁硫簇、类水红菊酯金属结合和 Kdp)。参与 SOS 反应的recA、umuDddrR基因也被上调。umuD的敲除显示持久细胞形成显着减少,而它们在recA突变株。研究中强调的差异表达基因值得进一步研究,作为有效控制鲍曼不动杆菌感染的治疗靶点。

更新日期:2021-11-29
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