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Modulation of Drug Resistance by Limonene: Inhibition of Efflux Pumps in Staphylococcus aureus Strains RN-4220 and IS-58

Author(s):

Ana Carolina Justino de Araújo, Priscilla Ramos Freitas, Cristina Rodrigues dos Santos Barbosa, Débora Feitosa Muniz, Jaime Jaime Ribeiro-Filho, Saulo Relison Tintino, José Pinto Siqueira Júnior, José Maria Barbosa Filho, Gabriela Ribeiro de Sousa and Henrique Douglas Melo Coutinho*   Pages 1 - 6 ( 6 )

Abstract:


Aims: This study aimed to investigate the potential of limonene as an efflux pump (EP) inhibitor in Staphylococcus aureus strains RN-4220 and IS-58, which carry EPs for erythromycin (MrsA) and tetracycline (TetK), respectively.

Background: The evolution of bacterial resistance mechanisms over time has impaired the action of most classes of antibiotics. Staphylococcus aureus is a notable bacterium, with high pathogenic potential and demonstrated resistance to conventional antibiotics. Considering the importance of discovering novel compounds to combat antibiotic resistance, our group previously demonstrated the antibacterial properties of limonene, a compound present in the essential oils of several plant species.

Objective: This study aimed to investigate the potential of limonene as an efflux pump (EP) inhibitor in Staphylococcus aureus strains RN-4220 and IS-58, which carry EPs for erythromycin (MrsA) and tetracycline (TetK), respectively.

Method: The minimum inhibitory concentrations (MIC) of limonene and other efflux pump inhibitors were determined through the broth microdilution method. A reduction in the MIC of ethidium bromide was used as a parameter of EP inhibition.

Result: While limonene was not shown to exhibit direct antibacterial effects against EP-carrying strains, in association with ethidium bromide and antibiotics, this compound demonstrated enhanced antibacterial activity, indicating the inhibition of the MrsA and TetK pumps.

Conclusion: In conclusion, this pioneering study demonstrated the effectiveness of limonene as an EP inhibitor in S. aureus strains RN-4220 and IS-58. Nevertheless, further studies are required to characterize the molecular mechanisms associated with limonene-mediated EP inhibition.

Keywords:

Staphylococcus aureus, Limonene, Bacterial resistance, Efflux pump inhibitors, Ethidium bromide, Antibacterial

Affiliation:

Department of Biological Chemistry, Regional University of Cariri, URCA, Crato, CE,, Department of Biological Chemistry, Regional University of Cariri, URCA, Crato, CE,, Department of Biological Chemistry, Regional University of Cariri, URCA, Crato, CE,, Department of Biological Chemistry, Regional University of Cariri, URCA, Crato, CE,, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, IGM-FIOCRUZ/BA, Salvador, BA,, Department of Biological Chemistry, Regional University of Cariri, URCA, Crato, CE,, Federal University of Paraíba – UFPB, João Pessoa, Paraíba,, Federal University of Paraíba – UFPB, João Pessoa, Paraíba,, Federal University of Paraíba – UFPB, João Pessoa, Paraíba,, Department of Biological Chemistry, Regional University of Cariri, URCA, Crato, CE



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