{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:46:47Z","timestamp":1790120807246,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSPD2023R709"],"award-info":[{"award-number":["RSPD2023R709"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["DCT-0182-00104.02.00\/21"],"award-info":[{"award-number":["DCT-0182-00104.02.00\/21"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["04855159\/2022"],"award-info":[{"award-number":["04855159\/2022"]}]},{"name":"Cearense Foundation for Supporting Scientific and Technological Development (FUNCAP)","award":["RSPD2023R709"],"award-info":[{"award-number":["RSPD2023R709"]}]},{"name":"Cearense Foundation for Supporting Scientific and Technological Development (FUNCAP)","award":["DCT-0182-00104.02.00\/21"],"award-info":[{"award-number":["DCT-0182-00104.02.00\/21"]}]},{"name":"Cearense Foundation for Supporting Scientific and Technological Development (FUNCAP)","award":["04855159\/2022"],"award-info":[{"award-number":["04855159\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u03b1-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 \u00b5g\/mL against the S. aureus RN4220 strain. Isolated nerolidol stood out for reducing the MIC of EtBr to 5 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/molecules28227649","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T15:30:53Z","timestamp":1700235053000},"page":"7649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and \u03b1-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1088-9910","authenticated-orcid":false,"given":"Jorge Ederson Gon\u00e7alves","family":"Santana","sequence":"first","affiliation":[{"name":"Departamento de Antibi\u00f3ticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-7064","authenticated-orcid":false,"given":"C\u00edcera Datiane de Morais","family":"Oliveira-Tintino","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-035X","authenticated-orcid":false,"given":"Gabriel","family":"Gon\u00e7alves Alencar","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-3064","authenticated-orcid":false,"given":"Gustavo Miguel","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5307-5049","authenticated-orcid":false,"given":"Daniel","family":"Sampaio Alves","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8750-6626","authenticated-orcid":false,"given":"Talysson Felismino","family":"Moura","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7733-9331","authenticated-orcid":false,"given":"Saulo Relison","family":"Tintino","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-9581","authenticated-orcid":false,"given":"Irwin Rose Alencar","family":"de Menezes","sequence":"additional","affiliation":[{"name":"Departament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-6215","authenticated-orcid":false,"given":"Jo\u00e3o Pedro Viana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Oswaldo Cruz Foundation (Fiocruz Cear\u00e1), Eusebio 61773-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4801-7189","authenticated-orcid":false,"given":"Vanessa Barbosa Pinheiro","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Oswaldo Cruz Foundation (Fiocruz Cear\u00e1), Eusebio 61773-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6101-1155","authenticated-orcid":false,"given":"Roberto","family":"Nicolete","sequence":"additional","affiliation":[{"name":"Oswaldo Cruz Foundation (Fiocruz Cear\u00e1), Eusebio 61773-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2272","authenticated-orcid":false,"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA"},{"name":"Legorreta Cancer Center, Brown University, Providence, RI 02912, USA"},{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3150-9139","authenticated-orcid":false,"given":"Clara 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