Abstract

The antibacterial activity and efflux pump reversal of thymol and carvacrol were investigated against the Staphylococcus aureus IS-58 strain in this study, as well as their toxicity against Drosophila melanogaster. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, while efflux pump inhibition was assessed by reduction of the antibiotic and ethidium bromide (EtBr) MICs. D. melanogaster toxicity was tested using the fumigation method. Both thymol and carvacrol presented antibacterial activities with MICs of 72 and 256 µg/mL, respectively. The association between thymol and tetracycline demonstrated synergism, while the association between carvacrol and tetracycline presented antagonism. The compound and EtBr combinations did not differ from controls. Thymol and carvacrol toxicity against D. melanogaster were evidenced with EC50 values of 17.96 and 16.97 µg/mL, respectively, with 48 h of exposure. In conclusion, the compounds presented promising antibacterial activity against the tested strain, although no efficacy was observed in terms of efflux pump inhibition.

Highlights

  • The prevalence of bacterial resistance to antibiotics, this being associated with increased mortality rates, has become a source of great concern for public health [1]

  • When the antibiotic was tested in association with standard inhibitors, the Minimum Inhibitory Concentration (MIC)

  • With respect to efflux pump inhibition, the assays with ethidium bromide (EtBr) as a pump substrate found the association between thymol and EtBr did not differ from the control

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Summary

Introduction

The prevalence of bacterial resistance to antibiotics, this being associated with increased mortality rates, has become a source of great concern for public health [1]. There are several mechanisms by which S. aureus develops resistance to antimicrobials, including limited drug absorption, target modification, enzymatic inactivation and active efflux mechanisms [4]. The latter, known as efflux pumps, are proteins integrated into the bacterial plasma membrane that reduce the intracellular concentration of antibiotics by extruding them from the cell [5]. Among these pumps, the TetK pump, belonging to the major facilitator superfamily (MFS), is present in S. aureus IS-58 strain. TetK powers its transport activity with energy derived from proton gradients and is responsible for resistance to the tetracycline class of antibiotics [6]

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