Repurposing approved drugs as potential efflux pump inhibitors in multidrug-resistant Pseudomonas aeruginosa .
Gláucia Morgana de Melo GuedesVinícius Carvalho PereiraAlyne Soares FreitasPaulo Roberto Honório de SouzaAura Lucia Chacon ParraJaiane Alves BrasilRodrigo Fonseca de Medeiros GuedesPaulo César Pereira de SousaRossana de Aguiar CordeiroMarcos Fábio Gadelha RochaJosé Júlio da Costa SidrimDébora de Souza Collares Maia Castelo-BrancoPublished in: Future microbiology (2024)
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.
Keyphrases
- multidrug resistant
- pseudomonas aeruginosa
- antimicrobial resistance
- induced apoptosis
- acinetobacter baumannii
- cell cycle arrest
- gram negative
- candida albicans
- cystic fibrosis
- drug resistant
- biofilm formation
- endoplasmic reticulum stress
- cell death
- signaling pathway
- staphylococcus aureus
- cell proliferation
- single cell
- pi k akt