Valencene, Nootkatone and Their Liposomal Nanoformulations as Potential Inhibitors of NorA, Tet(K), MsrA, and MepA Efflux Pumps in Staphylococcus aureus Strains
-
Published:2023-09-28
Issue:10
Volume:15
Page:2400
-
ISSN:1999-4923
-
Container-title:Pharmaceutics
-
language:en
-
Short-container-title:Pharmaceutics
Author:
Oliveira-Tintino Cícera Datiane de Morais1ORCID, Santana Jorge Ederson Gonçalves2, Alencar Gabriel Gonçalves1ORCID, Siqueira Gustavo Miguel1, Gonçalves Sheila Alves1, Tintino Saulo Relison1ORCID, Menezes Irwin Rose Alencar de1ORCID, Rodrigues João Pedro Viana3ORCID, Gonçalves Vanessa Barbosa Pinheiro3, Nicolete Roberto3ORCID, Ribeiro-Filho Jaime3ORCID, da Silva Teresinha Gonçalves2, Coutinho Henrique Douglas Melo1ORCID
Affiliation:
1. Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-010, CE, Brazil 2. Department of Antibiotics, Federal University of Pernambuco (UFPE), Recife 50670-901, PE, Brazil 3. Oswaldo Cruz Foundation (Fiocruz Ceará), Eusébio 61773-270, CE, Brazil
Abstract
Valencene and nootkatone are aromatic sesquiterpenes with known biological activities, such as antimicrobial, antioxidant, anti-inflammatory, and antitumor. Given the evidence that encapsulation into nanosystems, such as liposomes, could improve the properties of several compounds, the present study aimed to evaluate the activity of these sesquiterpenes in their isolated state or in liposomal formulations against strains of Staphylococcus aureus carrying efflux pumps. The broth microdilution method evaluated the antibiotic-enhancing activity associated with antibiotics and ethidium bromide (EtBr). The minimum inhibitory concentration was assessed in strains of S. aureus 1199B, IS-58, and RN4220, which carry the efflux proteins NorA, Tet(K), and MsrA. In tests with strain 1199B, valencene reduced the MIC of norfloxacin and EtBr by 50%, while the liposomal formulation of this compound did not show a significant effect. Regarding the strain IS-58, valencene, and its nanoformulation reduced norfloxacin MIC by 60.3% and 50%, respectively. In the non-liposomal form, the sesquiterpene reduced the MIC of EtBr by 90%. Against the RN4220 strain, valencene reduced the MIC of the antibiotic and EtBr by 99% and 93.7%, respectively. Nootkatone and its nanoformulation showed significant activity against the 1199B strain, reducing the EtBr MIC by 21.9%. Against the IS-58 strain, isolated nootkatone reduced the EtBr MIC by 20%. The results indicate that valencene and nootkatone potentiate the action of antibiotics and efflux inhibitors in strains carrying NorA, Tet(K), and MsrA proteins, which suggests that these sesquiterpenes act as efflux pump inhibitors in S. aureus. Therefore, further studies are needed to assess the impact of incorporation into liposomes on the activity of these compounds in vivo.
Funder
Foundation for Supporting Scientific and Technological Development
Subject
Pharmaceutical Science
Reference58 articles.
1. Epidemiology and Burden of Multidrug-Resistant Bacterial Infection in a Developing Country;Lim;eLife,2016 2. Epidemiology and Risk Factors Associated with Mortality in Consecutive Patients with Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria;Santoro;Open Forum. Infect. Dis.,2020 3. Treatment of Staphylococcus aureus Infections;David;Curr. Top. Microbiol. Immunol.,2017 4. Library, W.O. (2016). Rook’s Textbook of Dermatology, Oxford University Press (OUP). [9th ed.]. 5. Guo, Y., Song, G., Sun, M., Wang, J., and Wang, Y. (2020). Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureus. Front. Cell Infect. Microbiol., 10.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|