Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations
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. Th...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/22/7649 |
| _version_ | 1797458182848643072 |
|---|---|
| author | Jorge Ederson Gonçalves Santana Cícera Datiane de Morais Oliveira-Tintino Gabriel Gonçalves Alencar Gustavo Miguel Siqueira Daniel Sampaio Alves Talysson Felismino Moura Saulo Relison Tintino Irwin Rose Alencar de Menezes João Pedro Viana Rodrigues Vanessa Barbosa Pinheiro Gonçalves Roberto Nicolete Talha Bin Emran Clara Mariana Gonçalves Lima Sheikh F. Ahmad Henrique Douglas Melo Coutinho Teresinha Gonçalves da Silva |
| author_facet | Jorge Ederson Gonçalves Santana Cícera Datiane de Morais Oliveira-Tintino Gabriel Gonçalves Alencar Gustavo Miguel Siqueira Daniel Sampaio Alves Talysson Felismino Moura Saulo Relison Tintino Irwin Rose Alencar de Menezes João Pedro Viana Rodrigues Vanessa Barbosa Pinheiro Gonçalves Roberto Nicolete Talha Bin Emran Clara Mariana Gonçalves Lima Sheikh F. Ahmad Henrique Douglas Melo Coutinho Teresinha Gonçalves da Silva |
| author_sort | Jorge Ederson Gonçalves Santana |
| collection | DOAJ |
| description | 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 <i>Staphylococcus aureus</i> 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: <i>S. aureus</i> 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 <i>S. aureus</i> 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. |
| first_indexed | 2024-03-09T16:34:24Z |
| format | Article |
| id | doaj.art-8369be72e81845e5a64630f56d8c0cfa |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:34:24Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8369be72e81845e5a64630f56d8c0cfa2023-11-24T14:58:33ZengMDPI AGMolecules1420-30492023-11-012822764910.3390/molecules28227649Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal NanoformulationsJorge Ederson Gonçalves Santana0Cícera Datiane de Morais Oliveira-Tintino1Gabriel Gonçalves Alencar2Gustavo Miguel Siqueira3Daniel Sampaio Alves4Talysson Felismino Moura5Saulo Relison Tintino6Irwin Rose Alencar de Menezes7João Pedro Viana Rodrigues8Vanessa Barbosa Pinheiro Gonçalves9Roberto Nicolete10Talha Bin Emran11Clara Mariana Gonçalves Lima12Sheikh F. Ahmad13Henrique Douglas Melo Coutinho14Teresinha Gonçalves da Silva15Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilOswaldo Cruz Foundation (Fiocruz Ceará), Eusebio 61773-270, BrazilOswaldo Cruz Foundation (Fiocruz Ceará), Eusebio 61773-270, BrazilOswaldo Cruz Foundation (Fiocruz Ceará), Eusebio 61773-270, BrazilDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USADepartment of Food Science, Federal University of Lavras, Lavras 37203-202, BrazilDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartament of Biological Chemistry, Universidade Regional do Cariri (URCA), Crato 63105-010, BrazilDepartamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, BrazilThe 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 <i>Staphylococcus aureus</i> 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: <i>S. aureus</i> 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 <i>S. aureus</i> 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.https://www.mdpi.com/1420-3049/28/22/7649efflux pumpfluorescenceliposomenanoformulationsesquiterpenes<i>Staphylococcus aureus</i> |
| spellingShingle | Jorge Ederson Gonçalves Santana Cícera Datiane de Morais Oliveira-Tintino Gabriel Gonçalves Alencar Gustavo Miguel Siqueira Daniel Sampaio Alves Talysson Felismino Moura Saulo Relison Tintino Irwin Rose Alencar de Menezes João Pedro Viana Rodrigues Vanessa Barbosa Pinheiro Gonçalves Roberto Nicolete Talha Bin Emran Clara Mariana Gonçalves Lima Sheikh F. Ahmad Henrique Douglas Melo Coutinho Teresinha Gonçalves da Silva Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations Molecules efflux pump fluorescence liposome nanoformulation sesquiterpenes <i>Staphylococcus aureus</i> |
| title | Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations |
| title_full | Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations |
| title_fullStr | Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations |
| title_full_unstemmed | Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations |
| title_short | Comparative Antibacterial and Efflux Pump Inhibitory Activity of Isolated Nerolidol, Farnesol, and α-Bisabolol Sesquiterpenes and Their Liposomal Nanoformulations |
| title_sort | comparative antibacterial and efflux pump inhibitory activity of isolated nerolidol farnesol and α bisabolol sesquiterpenes and their liposomal nanoformulations |
| topic | efflux pump fluorescence liposome nanoformulation sesquiterpenes <i>Staphylococcus aureus</i> |
| url | https://www.mdpi.com/1420-3049/28/22/7649 |
| work_keys_str_mv | AT jorgeedersongoncalvessantana comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT ciceradatianedemoraisoliveiratintino comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT gabrielgoncalvesalencar comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT gustavomiguelsiqueira comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT danielsampaioalves comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT talyssonfelisminomoura comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT saulorelisontintino comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT irwinrosealencardemenezes comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT joaopedrovianarodrigues comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT vanessabarbosapinheirogoncalves comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT robertonicolete comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT talhabinemran comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT claramarianagoncalveslima comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT sheikhfahmad comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT henriquedouglasmelocoutinho comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations AT teresinhagoncalvesdasilva comparativeantibacterialandeffluxpumpinhibitoryactivityofisolatednerolidolfarnesolandabisabololsesquiterpenesandtheirliposomalnanoformulations |