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铜诱导鲍曼不动杆菌MCC 3114抗生素耐药性增强。

Copper induced augmentation of antibiotic resistance in Acinetobacter baumannii MCC 3114.

作者信息

Chauhan Ravi, Patel Hardi, Bhardwaj Bhavna, Suryawanshi Vijay, Rawat Seema

机构信息

Microbiology Lab, School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat, 382030, India.

出版信息

Biometals. 2025 Apr;38(2):485-504. doi: 10.1007/s10534-024-00657-3. Epub 2024 Dec 21.

Abstract

Increasing antibiotic resistance among the common nosocomial pathogen i.e. Acinetobacter baumannii poses life threat to the health care workers as well as to the society. The dissemination of antibiotic resistance in this pathogen at an alarming rate could be not only due to the overuse of antibiotics but also due to the stress caused by exposure of bacterium to several environmental contaminants in their niches. In the present study, effect of copper stress on augmentation in the antibiotic resistance of A. baumannii MCC 3114 against three clinically used antibiotics was investigated along with the phenotypic and genotypic alterations in the cell. It induced 8, 44 and 22-fold increase in resistance against colistin, ciprofloxacin and levofloxacin, respectively. Moreover, the biofilm formation of adapted culture was significantly enhanced due to a dense EPS around the cell (as revealed by SEM images). The structural changes in EPS were demonstrated by FTIR spectroscopy. The adequate growth of adapted MCC 3114 despite increased level of ROS indicates its persistence in copper and ROS stress. The physiological alterations in cell viz., increased efflux pump activity and decreased membrane permeability was observed. Molecular analysis revealed increased expression of efflux pump related genes, oxidative stress genes, integron and antibiotic resistance genes. In sum, our study revealed that the exposure of the critical pathogen, A. baunmannii to copper in hospital settings and environmental reservoirs can impose adaptive pressure which may lead to genotypic as well phenotypic changes in cell resulting into the augmentation of antibiotic resistance.

摘要

常见医院病原体鲍曼不动杆菌的抗生素耐药性不断增加,对医护人员乃至社会的健康构成了生命威胁。这种病原体中抗生素耐药性以惊人速度传播,不仅可能是由于抗生素的过度使用,还可能是由于细菌在其生存环境中接触多种环境污染物所造成的压力。在本研究中,研究了铜胁迫对鲍曼不动杆菌MCC 3114针对三种临床常用抗生素的耐药性增强的影响,以及细胞的表型和基因型改变。它分别使对黏菌素、环丙沙星和左氧氟沙星的耐药性提高了8倍、44倍和22倍。此外,由于细胞周围密集的胞外聚合物(如扫描电镜图像所示),适应培养物的生物膜形成显著增强。傅里叶变换红外光谱法证实了胞外聚合物的结构变化。尽管活性氧水平升高,但适应后的MCC 3114仍能充分生长,表明其在铜和活性氧胁迫下具有持久性。观察到细胞的生理变化,即外排泵活性增加和膜通透性降低。分子分析显示外排泵相关基因、氧化应激基因、整合子和抗生素耐药基因的表达增加。总之,我们的研究表明,医院环境和环境储库中的关键病原体鲍曼不动杆菌暴露于铜会施加适应性压力,这可能导致细胞的基因型和表型变化,从而增强抗生素耐药性。

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