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Evaluation of the inhibitory effect of isopulegol (ISO) and its β-cyclodextrin inclusion complex (ISO/β-CD) on the reversal of Staphylococcus aureus efflux pump activity

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Abstract

Staphylococcus aureus is known to be a human pathogen and is often resistant to antibiotics, so there is a demand for new treatment alternatives that have the ability to reverse such resistance. The present study aimed to evaluate the antibacterial action and reversal of the efflux pump activity of the compounds Isopulegol (ISO) and its β-cyclodextrin inclusion complex (ISO/β-CD) in S. aureus strains carrying an efflux pump. (MsrA, TetK, NorA and MepA). The complex was obtained using the paste complexation method. The minimum inhibitory concentration (MIC) of ISO and ISO/β-CD was determined for the evaluation of antibacterial activity against multiresistant strains of S. aureus (RN4220, IS-58, 1199, 1199B and K2068) and the compounds showed a minimum inhibitory concentration (MIC) ≥ 1024 μg/mL. Modulation assays were performed using ISO and ISO/β-CD, which associated with antibiotics and Ethidium Bromide (EtBr) showed synergism and MIC reduction in some of the tested bacteria. Therefore, it can be concluded that the isolated compounds ISO and ISO/β-CD are effective in inhibiting the efflux pump mechanism against some of the tested strains; with modulation, only strains IS-58, SA 1199 and K2068 showed a MIC decrease effect, while all strains showed a reduction in MIC with ethidium bromide.

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Acknowledgements

The University Regional of Cariri, to the pharmacology and molecular chemistry and microbiology and molecular chemistry laboratories for carrying out the tests and to the development networks for all financial support.

Funding

This work was supported by Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Financiadora de Estudos e Projetos—Brasil (FINEP).

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Authors and Affiliations

  1. Department of Biological Chemistry, Regional University of Cariri, Crato, CE, 63105-000, Brazil

    Lucas Yure Santos da Silva, Daniel Sampaio Alves, Andreza Guedes Barbosa Ramos, Renata Torres Pessoa, José Bezerra de Araújo-Neto, Maria Milene Costa da Silva, Isabel Sousa Alcântara, Luiz Jardelino de Lacerda Neto, Maria Rayane Correia de Oliveira, Cícera Datiane de Morais Oliveira-Tintino, Henrique Douglas Melo Coutinho & Irwin Rose Alencar de Menezes

  2. Department of Physiology, Federal University of Sergipe, São Cristóvão, Aracaju, SE, 49100-000, Brazil

    Lucindo José Quintans-Júnior

  3. Department of Agricultural and Environmental Sciences, Milan State University, 20133, Milan, Italy

    Marcello Iriti

Authors
  1. Lucas Yure Santos da Silva
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  2. Daniel Sampaio Alves
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Contributions

All authors contributed to the conception and design of the study. Tests and data analysis were performed by LYSS, AGBR, RTP, JBAN, MMCS, CDM OT. The Isopulegol complex was provided by Professor LJQJ. The first version of the manuscript was revised by LJLN, MRCO and ISA. The final version of the manuscript was reviewed by Professors HDMC and IRAM. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Henrique Douglas Melo Coutinho, Marcello Iriti or Irwin Rose Alencar de Menezes.

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da Silva, L.Y.S., Alves, D.S., Ramos, A.G.B. et al. Evaluation of the inhibitory effect of isopulegol (ISO) and its β-cyclodextrin inclusion complex (ISO/β-CD) on the reversal of Staphylococcus aureus efflux pump activity. Polym. Bull. (2024). https://doi.org/10.1007/s00289-024-05191-3

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