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Objective <p><i>Staphylococcus aureus</i> is a microorganism that can behave as a commensal or as a life-threatening pathogen. Its remarkable capacity to acquire resistance to antimicrobial agents, particularly through mechanisms such as efflux pumps, places it among the major contributors to global morbidity and mortality. In this study, the acyclic diterpene phytol was investigated for its potential as an efflux pump inhibitor (EPI). Molecular docking was performed to evaluate its interaction with the QacA/B efflux pump, followed by <i>in silico</i> prediction of ADMET properties. In addition, the inhibitory effect of phytol on efflux activity was assessed <i>in vitro</i> against <i>S. aureus</i>.</p> Methods <p>To this end, the Minimum Inhibitory Concentration (MIC) was determined through serial microdilution in broth. The evaluation of efflux pump inhibition was assessed by measuring the reduction in MIC of ampicillin and ethidium bromide (EtBr) when combined with phytol at sub-inhibitory concentrations (MIC/8).</p> Results <p>Docking results showed that phytol has an average binding affinity of -4.7&#xa0;kcal/mol with QacA, interacting with several amino acids at the binding site, additionally, the ADMET evaluation reveals Phytol as a promising compound for demonstrating low toxicological capacity.</p> Conclusions <p>However, despite the <i>in silico</i> interactions, the diterpene did not demonstrate direct antibacterial activity nor did it reduce the MIC of ampicillin or ethidium bromide, indicating that it does not function as an EPI.</p>

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Investigation of Phytol as an Inhibitor of the Efflux Pump (QacA/B) in Staphylococcus aureus: in silico and in vitro Studies

  • 期刊论文

  • 发表日期：

    2025年12月10日

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  • José Weverton Almeida-Bezerra,
  • Carlos Alonso Leite dos Santos,
  • Saulo Almeida Menezes,
  • Cícera Datiane de Morais Oliveira-Tintino,
  • Rafael Pereira da Cruz,
  • Adrielle Rodrigues Costa,
  • Janaína Esmeraldo Rocha,
  • Daniel Sampaio Alves,
  • Simone Galdino de Sousa,
  • Ewerton Yago de Sousa Rodrigues,
  • Gabriel Gonçalves Alencar,
  • José Maria Barbosa Filho,
  • Viviane Bezerra da Silva,
  • Saulo Relison Tintino,
  • Irwin Rose Alencar de Menezes,
  • José Thyálisson da Costa Silva,
  • Maria Flaviana Bezerra Morais-Braga,
  • Henrique Douglas Melo Coutinho

摘要

Objective

Staphylococcus aureus is a microorganism that can behave as a commensal or as a life-threatening pathogen. Its remarkable capacity to acquire resistance to antimicrobial agents, particularly through mechanisms such as efflux pumps, places it among the major contributors to global morbidity and mortality. In this study, the acyclic diterpene phytol was investigated for its potential as an efflux pump inhibitor (EPI). Molecular docking was performed to evaluate its interaction with the QacA/B efflux pump, followed by in silico prediction of ADMET properties. In addition, the inhibitory effect of phytol on efflux activity was assessed in vitro against S. aureus.

Methods

To this end, the Minimum Inhibitory Concentration (MIC) was determined through serial microdilution in broth. The evaluation of efflux pump inhibition was assessed by measuring the reduction in MIC of ampicillin and ethidium bromide (EtBr) when combined with phytol at sub-inhibitory concentrations (MIC/8).

Results

Docking results showed that phytol has an average binding affinity of -4.7 kcal/mol with QacA, interacting with several amino acids at the binding site, additionally, the ADMET evaluation reveals Phytol as a promising compound for demonstrating low toxicological capacity.

Conclusions

However, despite the in silico interactions, the diterpene did not demonstrate direct antibacterial activity nor did it reduce the MIC of ampicillin or ethidium bromide, indicating that it does not function as an EPI.