Abstract
BackgroundBacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli) strains, and to evaluate potential interaction.MethodsAntimicrobial susceptibility, minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken.ResultsFor total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625). Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein.ConclusionsOur results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains.Graphical abstractSynergistic effect of eugenol with colistin against colistin-resistant Escherichia coli isolates.
Highlights
Bacterial infections have become more challenging to treat due to the emergence of multidrugresistant pathogenic bacteria
Antimicrobial susceptibility test According to the obtained results, the thirteen clinical E. coli isolates were resistant to selected antibiotics to varying degrees
Time-kill analysis of eugenol Based on the results of minimum inhibitory concentration (MIC) assay, the time-kill curve was used to describe the viability after treated with eugenol
Summary
Bacterial infections have become more challenging to treat due to the emergence of multidrugresistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli) strains, and to evaluate potential interaction. It is urgently needed to find effective combination therapy and antibiotic succedaneum to Essential oils (EOs) are naturally derived from many plants with a series of pharmacological activities and have been widely used in traditional medicine and food preservation. A phenylpropanoid found in many plants and the major active essential oil component of clove, has been reported to have antioxidant properties, protective effect on the cardiovascular system, antibacterial and antifungal effect in previous studies
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