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. 2018 Jan 29:7:17.
doi: 10.1186/s13756-018-0303-7. eCollection 2018.

Synergistic effect of eugenol with Colistin against clinical isolated Colistin-resistant Escherichia coli strains

Yi-Ming Wang  1 , Ling-Cong Kong  1 , Jie Liu  1 , Hong-Xia Ma  1
Affiliations

Synergistic effect of eugenol with Colistin against clinical isolated Colistin-resistant Escherichia coli strains

Yi-Ming Wang et al. Antimicrob Resist Infect Control. .

Abstract

Background: Bacterial 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.

Methods: Antimicrobial 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.

Results: For 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.

Conclusions: Our 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.

Keywords: colistin-resistant Escherichia coli; eugenol; mcr-1 gene; molecular docking.

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Conflict of interest statement

Not applicableNot applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Effect of eugenol(control and MIC) on the viability of E. coli strains
Fig. 2
Fig. 2
Relative expression of mcr-1 gene. E. coli Po1 + MHB, E. coli Po1 + Eugenol (a), E. coli Po2 + MHB, E. coli Po2 + Eugenol (b), E. coli Po3 + MHB, E. coli Po3 + Eugenol (c), E. coli Go3 + MHB, E. coli Go3 + Eugenol (d), E. coli Go4 + MHB, E. coli Go4 + Eugenol (e), E. coli Bo+MHB, E. coli Bo+Eugenol (f). All data were expressed as mean ± S.D.,n = 3. ** P < 0.01, * P < 0.05 vs. non-synergy group
Fig. 3
Fig. 3
Putative pattern of interaction between eugenol and MCR-1 protein. The structure eugenol was shown in gray, the green stick around eugenol are amino acid residue. Carbon atoms were shown in gray, hydrogen atoms in white, oxygen atoms in red, nitrogen atoms in blue, sulphur atoms in gamboges
See this image and copyright information in PMC

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