Contribution of efflux activity in resistance to antibiotics in Escherichia coli clinical isolates

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy Pub Date : 2025-05-01 DOI:10.1016/j.jiac.2025.102725

Zahra Lotfian , Hossein Hosseini Nave , Razieh Khalili , Fereshteh Saffari

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引用次数: 0

Abstract

Background

In an attempt to find new therapeutic strategies for multidrug-resistant infections, understanding the contribution of efflux pumps is of particular importance. This study aimed to determine the contribution of efflux pumps in development of resistance to different classes of antibiotics in clinical isolates of E. coli in order to adopt more effective strategies in the treatment of related infections.

Methods

Two methods, i.e. measurement the expression level of some efflux related genes and assessment of efflux activity by H33342 accumulation assay using CCCP as an efflux inhibitor, were applied. The relationship of efflux activity with antibiotic resistance, was evaluated using three criteria including HA (dye accumulation in the absence of CCCP), HAC (dye accumulation in the presence of CCCP) and HAR (HAC/HA).

Results

Expression of tolC in ceftazidime, cefotaxime and azithromycin resistant groups and expression of acrA and mdfA in tetracycline resistant isolates were significantly higher than susceptible ones (p < 0.05). By investigating the simultaneous meeting of three proposed criteria for any studied antibiotics, no significant association was found between efflux activity and antibiotic resistance.

Conclusion

Finding a relation between the overexpression of some efflux genes and resistance to tetracycline, azithromycin and beta-lactams, confirmed the role of these pumps in resistance to mentioned antibiotics and highlighted the neglected role of efflux pumps in resistance to beta-lactams. Meeting two criteria in >70% of investigated antibiotics, confirmed the contribution of efflux as a partial resistance mechanism in these isolates.

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外排活性在大肠杆菌临床分离株抗生素耐药性中的作用

背景为了寻找耐多药感染的新治疗策略，了解外排泵的作用尤为重要。本研究旨在确定外排泵在大肠杆菌临床分离株对不同种类抗生素产生耐药性中的作用，以便采取更有效的策略治疗相关感染。方法采用CCCP作为外排抑制剂，采用H33342积累法测定外排相关基因的表达水平和评估外排活性。外排活性与抗生素耐药性的关系采用三个标准进行评估，包括HA（无CCCP时的染料积累）、HAC（有CCCP时的染料积累）和HAR （HAC/HA）。结果头孢他啶、头孢噻肟和阿奇霉素耐药组中tolC的表达以及四环素耐药株中acrA和mdfA的表达均显著高于敏感株(p <；0.05)。通过调查同时满足所研究抗生素的三个拟议标准，没有发现外排活性与抗生素耐药性之间的显著关联。结论发现部分外排基因的过表达与四环素、阿奇霉素和β -内酰胺耐药之间存在相关性，证实了这些外排基因在上述抗生素耐药中的作用，并强调了外排基因在β -内酰胺耐药中的作用。70%被调查的抗生素符合两个标准，证实了外排作为这些分离株的部分耐药机制的贡献。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection and Chemotherapy INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY

CiteScore

4.10

自引率

4.50%

发文量

303

审稿时长

47 days

期刊介绍： The Journal of Infection and Chemotherapy (JIC) — official journal of the Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases — welcomes original papers, laboratory or clinical, as well as case reports, notes, committee reports, surveillance and guidelines from all parts of the world on all aspects of chemotherapy, covering the pathogenesis, diagnosis, treatment, and control of infection, including treatment with anticancer drugs. Experimental studies on animal models and pharmacokinetics, and reports on epidemiology and clinical trials are particularly welcome.