RESUMO
Efflux pump inhibitors are a potential therapeutic strategy for managing antimicrobial resistance and biofilm formation. This article evaluated the effect of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on the biofilm growth dynamics and the production of virulence factors by Burkholderia pseudomallei. The effects of CCCP on planktonic, growing, and mature biofilm, interaction with antibacterial drugs, and protease and siderophore production were assessed. CCCP MICs ranged between 128 and 256 µM. The CCCP (128 µM) had a synergic effect with all the antibiotics tested against biofilms. Additionally, CCCP reduced (p < .05) the biomass of biofilm growth and mature biofilms at 128 and 512 µM, respectively. CCCP also decreased (p < .05) protease production by growing (128 µM) and induced (p < .05) siderophore release by planktonic cells (128 µM) growing biofilms (12.8 and 128 µM) and mature biofilms (512 µM). CCCP demonstrates potential as a therapeutic adjuvant for disassembling B. pseudomallei biofilms and enhancing drug penetration.
Assuntos
Antibacterianos , Biofilmes , Burkholderia pseudomallei , Carbonil Cianeto m-Clorofenil Hidrazona , Testes de Sensibilidade Microbiana , Peptídeo Hidrolases , Sideróforos , Biofilmes/efeitos dos fármacos , Sideróforos/farmacologia , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/fisiologia , Antibacterianos/farmacologia , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Peptídeo Hidrolases/metabolismo , Fatores de VirulênciaRESUMO
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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Assuntos
Antibacterianos , Biofilmes , Reposicionamento de Medicamentos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Prometazina/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Humanos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , HidrazonasRESUMO
AIM: To investigate the direct effect of antibiotics on growth and virulence of the major Candida species associated with invasive infections. MATERIALS & METHODS: Cefepime, imipenem, meropenem, amoxicillin and vancomycin were tested at twofold the peak plasma concentration (2× PP) and the peak plasma concentration (PP). The effects of antibiotics on Candida albicans, Candida parapsilosis, Candida krusei and Candida tropicalis were investigated by colony counting, flow cytometry, proteolytic activity and virulence in Caenorhabditis elegans. RESULTS: Antibiotics increase growth and proteolytic activity of Candida spp; In addition, amoxicillin potentiates virulence of C. krusei and C. tropicalis against Caenorhabditis elegans. CONCLUSION: These results suggest that antimicrobial therapy may have a direct effect on the pathophysiology of invasive fungal infections in patients at risk.