| Autor: |
Santana JEG; Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, Brazil., Oliveira-Tintino CDM; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., Gonçalves Alencar G; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., Siqueira GM; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., Sampaio Alves D; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., Moura TF; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., Tintino SR; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., de Menezes IRA; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., Rodrigues JPV; Oswaldo Cruz Foundation (Fiocruz Ceará), Eusebio 61773-270, Brazil., Gonçalves VBP; Oswaldo Cruz Foundation (Fiocruz Ceará), Eusebio 61773-270, Brazil., Nicolete R; Oswaldo Cruz Foundation (Fiocruz Ceará), Eusebio 61773-270, Brazil., Emran TB; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.; Legorreta Cancer Center, Brown University, Providence, RI 02912, USA.; Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh., Gonçalves Lima CM; Department of Food Science, Federal University of Lavras, Lavras 37203-202, Brazil., Ahmad SF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Coutinho HDM; Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil., da Silva TG; Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, Brazil. |
| Abstrakt: |
The efflux systems are considered important mechanisms of bacterial resistance due to their ability to extrude various antibiotics. Several naturally occurring compounds, such as sesquiterpenes, have demonstrated antibacterial activity and the ability to inhibit efflux pumps in resistant strains. Therefore, the objective of this research was to analyze the antibacterial and inhibitory activity of the efflux systems NorA, Tet(K), MsrA, and MepA by sesquiterpenes nerolidol, farnesol, and α-bisabolol, used either individually or in liposomal nanoformulation, against multi-resistant Staphylococcus aureus strains. The methodology consisted of in vitro testing of the ability of sesquiterpenes to reduce the Minimum Inhibitory Concentration (MIC) and enhance the action of antibiotics and ethidium bromide (EtBr) in broth microdilution assays. The following strains were used: S. aureus 1199B carrying the NorA efflux pump, resistant to norfloxacin; IS-58 strain carrying Tet(K), resistant to tetracyclines; RN4220 carrying MsrA, conferring resistance to erythromycin. For the EtBr fluorescence measurement test, K2068 carrying MepA was used. It was observed the individual sesquiterpenes exhibited better antibacterial activity as well as efflux pump inhibition. Farnesol showed the lowest MIC of 16.5 µg/mL against the S. aureus RN4220 strain. Isolated nerolidol stood out for reducing the MIC of EtBr to 5 µg/mL in the 1199B strain, yielding better results than the positive control CCCP, indicating strong evidence of NorA inhibition. The liposome formulations did not show promising results, except for liposome/farnesol, which reduced the MIC of EtBr against 1199B and RN4220. Further research is needed to evaluate the mechanisms of action involved in the inhibition of resistance mechanisms by the tested compounds. |
