In silico and in vitro evaluation of efflux pumps inhibition of α,β-amyrin
| Autor: | Raimundo Luiz Silva Pereira, Raissa C Oliveira, Carlos Emídio Sampaio Nogueira, Alexandre Magno Rodrigues Teixeira, Francisco N. Pereira-Junior, Priscila R. Freitas, Márcia Machado Marinho, Paulo Nogueira Bandeira, Hélcio Silva dos Santos, Henrique Douglas Melo Coutinho, Telma L. G. Lemos, Janaína Esmeraldo Rocha, Emmanuel Silva Marinho, Jackelyne Roberta Scherf, Emanuelle Machado Marinho, Thiago Sampaio de Freitas |
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| Rok vydání: | 2021 |
| Předmět: |
biology
medicine.drug_class Antibiotics General Medicine medicine.disease_cause biology.organism_classification chemistry.chemical_compound chemistry Biochemistry Structural Biology Staphylococcus aureus medicine Efflux Ethidium bromide Antibacterial activity Molecular Biology Escherichia coli Norfloxacin Bacteria medicine.drug |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 40:12785-12799 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | The use of the bacterial efflux pump mechanism to reduce the concentrations of antibiotics in the intracellular to the extracellular region is one of the main mechanisms by which bacteria acquire resistance to antibiotics. The present study aims to evaluate the antibacterial activity of the α,β-amyrin mixture isolated from Protium heptaphyllum against the multidrug-resistant strains of Escherichia coli 06 and Staphylococcus aureus 10, and to verify the inhibition of the efflux resistance mechanisms against the strains of S. aureus 1199B and K2068, carrying the NorA and MepA efflux pumps, respectively. The α,β-amyrin did not show clinically relevant direct bacterial activity. However, the α,β-amyrin when associated with the gentamicin antibiotic presented synergistic effect against the multidrug-resistant bacterial strain of S. aureus 10. In strains with efflux pumps, α,β-amyrin was able to inhibit the action of the efflux protein NorA against Ethidium Bromide. However, this inhibitory effect was not observed in the MepA efflux pump. In addition, when evaluating the effect of standard efflux pump inhibitors, clorptomazine and CCCP, α,β-amyrin showed a decrease in MIC, demonstrating the presence of the efflux mechanism through synergism. Docking studies indicate that α, β-amyrin have a higher affinity energy to MepA, and NorA than ciprofloxacin and norfloxacin. Also, α, β-amyrin bind to the same region of the binding site as these antibiotics. It was concluded that the α, β-amyrin has the potential to increase antibacterial activity with the association of antibiotics, together with the ability to be a strong candidate for an efflux pump inhibitor. Communicated by Ramaswamy H. Sarma |
| Databáze: | OpenAIRE |
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