Potentiation of Antibiotic Action and Efflux Pump Inhibitory Effect on Staphylococcus aureus Strains by Solasodine

茄索定对金黄色葡萄球菌菌株的抗生素作用和外排泵抑制作用增强

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作者:Ana Raquel Pereira da Silva, Maria do Socorro Costa, Nara Juliana Santos Araújo, Thiago Sampaio de Freitas, Ray Silva de Almeida, José Maria Barbosa Filho, Josean Fechine Tavares, Erlânio Oliveira de Souza, Pablo Antonio Maia de Farias, Jacqueline Cosmo Andrade Pinheiro, Henrique Douglas Melo Coutin

Abstract

A worrisome fact is the increase in microbial resistance, which has as its main cause the indiscriminate use of antibiotics. Scientific studies have investigated bioactive compounds such as steroidal sapogenins, in the perspective of new beneficial alternatives for the control of bacterial resistance. Therefore, the objective of this work was to verify the antibacterial activity as well as the modifying action of antibiotics associated with solasodine and its ability to inhibit the efflux pump mechanism in strains of Staphylococcus aureus. Tests were performed to verify the minimum inhibitory concentration (MIC). In addition, the action-modifying potential of antibiotics and the inhibitory capacity of the efflux pump NorA and MepA through synergistic effects on the antibiotic and ethidium bromide were evaluated. Solasodine showed significant results for the standard bacteria with an MIC of 512 μg/mL, and when associated with the antibiotics gentamicin and nofloxacin for the multidrug-resistant bacteria S. aureus 10, Escherichia coli 06, and Pseudomonas aeruginosa 24, it showed a 50% reduction in MIC. The association of solasodine with the antibiotic ciprofloxacin against S. aureus K2068 (MepA) showed synergism, with a reduction in the MIC of the antibiotic from 64 μg/mL to 40 μg/mL, and also a reduction in the MIC when the antibiotic was used in conjunction with the efflux pump inhibitors. Solasodine may be acting on the mechanism of action of the antibiotic, as it has shown a potentiating effect when associated with antibiotics, inducing a reduction in the MIC against Gram-positive and Gram-negative bacteria. Therefore, this study demonstrated significant results for the potentiating action of solasodine when associated with antibiotics of clinical importance.

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