Repurposing approved drugs as potential efflux pump inhibitors in multidrug-resistant Pseudomonas aeruginosa.

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-04-17 DOI:10.2217/fmb-2023-0208

Gláucia Morgana de Melo Guedes, V. C. Pereira, A. Freitas, Paulo Roberto Honório de Souza, Aura Lucia Chacon Parra, Jaiane Alves Brasil, Rodrigo Fonseca de Medeiros Guedes, Paulo César Pereira de Sousa, R. A. Aguiar Cordeiro, M. F. Gadelha Rocha, J. C. Costa Sidrim, Débora de Souza Collares Maia Castelo Branco

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Abstract

Aim: To evaluate the action of promethazine, fluoxetine and carbonyl cyanide 3-chlorophenylhydrazone as efflux pump inhibitors (EPIs) against multidrug-resistant Pseudomonas aeruginosa. Methods: The effect of the compounds was evaluated in planktonic cells and bacterial biofilms. Accumulation tests were performed with ethidium bromide to prove their action as EPIs. Then, they were associated with antimicrobials. Results: Effect on planktonic cells and biofilms was found. Assays with ethidium bromide indicate their action as EPIs. Significant reductions in the metabolic activity of biofilms were observed after the association with the antimicrobials, especially for meropenem. Conclusion: It is possible to prove the action of these compounds as EPIs for P. aeruginosa and demonstrate the relevance of efflux pumps in antimicrobial resistance.

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将已获批准的药物作为潜在的外排泵抑制剂重新用于耐多药铜绿假单胞菌。

目的：评估丙咪嗪、氟西汀和 3-氯苯基腙作为外排泵抑制剂（EPIs）对耐多药铜绿假单胞菌的作用。方法：在浮游细胞和细菌生物膜中评估了这些化合物的效果。用溴化乙锭进行了蓄积试验，以证明其作为 EPIs 的作用。然后，将这些化合物与抗菌剂结合起来。结果发现它们对浮游细胞和生物膜都有影响。用溴化乙锭进行的检测表明它们具有 EPIs 的作用。生物膜与抗菌素（尤其是美罗培南）结合后，其代谢活性显著降低。结论可以证明这些化合物对铜绿假单胞菌具有 EPI 作用，并证明了外排泵与抗菌药耐药性的相关性。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.