Effect of Carvacrol and Thymol on NorA efflux pump inhibition in multidrug-resistant (MDR) Staphylococcus aureus strains.

Autor: Dos Santos Barbosa CR; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil. hdmcoutinho@gmail.com., Scherf JR; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil., de Freitas TS; Laboratory of Simulations and Molecular Spectroscopy (Lasemol), Regional University of Cariri-URCA, Crato, Brazil., de Menezes IRA; Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri-URCA, Crato, Brazil., Pereira RLS; Laboratory of Simulations and Molecular Spectroscopy (Lasemol), Regional University of Cariri-URCA, Crato, Brazil., Dos Santos JFS; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil., de Jesus SSP; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil., Lopes TP; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil., de Sousa Silveira Z; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil., de Morais Oliveira-Tintino CD; Laboratory of Pharmacotoxicological Prospection of Bioactive Products (Biofarmatox), Federal University of Pernambuco-UFPE, Recife, Brazil., Júnior JPS; Laboratory of Microorganism Genetics (LGM), Federal University of Paraiba-UFPB, João Pessoa, Brazil., Coutinho HDM; Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri-URCA, Crato, Brazil. hdmcoutinho@gmail.com., Tintino SR; Laboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri-URCA, Crato, Brazil., da Cunha FAB; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Regional University of Cariri-URCA, Crato, Brazil. cunha.urca@gmail.com.
Jazyk: angličtina
Zdroj: Journal of bioenergetics and biomembranes [J Bioenerg Biomembr] 2021 Aug; Vol. 53 (4), pp. 489-498. Date of Electronic Publication: 2021 Jun 22.
DOI: 10.1007/s10863-021-09906-3
Abstrakt: Undue exposure to antimicrobials has led to the acquisition and development of sophisticated bacterial resistance mechanisms, such as efflux pumps, which are able to expel or reduce the intracellular concentration of various antibiotics, making them ineffective. Therefore, inhibiting this mechanism is a promising way to minimize the phenomenon of resistance in bacteria. In this sense, the present study sought to evaluate the activity of the Carvacrol (CAR) and Thymol (THY) terpenes as possible Efflux Pump Inhibitors (EPIs), by determining the Minimum Inhibitory Concentration (MIC) and the association of these compounds in subinhibitory concentrations with the antibiotic Norfloxacin and with Ethidium Bromide (EtBr) against strains SA-1199 (wild-type) and SA-1199B (overexpresses NorA) of Staphylococcus aureus. In order to verify the interaction of the terpenes with the NorA efflux protein, an in silico molecular modeling study was carried out. The assays used to obtain the MIC of CAR and THY were performed by broth microdilution, while the Efflux Pump inhibitory test was performed by the MIC modification method of the antibiotic Norfloxacin and EtBr. docking was performed using the Molegro Virtual Docker (MVD) program. The results of the study revealed that CAR and THY have moderate bacterial activity and are capable of reducing the MIC of Norfloxacin antibiotic and EtBr in strains of S. aureus carrying the NorA efflux pump. The docking results showed that these terpenes act as possible competitive NorA inhibitors and can be investigated as adjuvants in combined therapies aimed at reducing antibiotic resistance.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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