Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance

Li Liu,Jingyi Yu,Fangyou Yu,Xingwei Cao,Yinjuan Guo,Qing Zhan,Xiaofei Shen

doi:10.1186/s12866-020-01995-1

Abstract

BackgroundMultidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. In this study, we selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect.ResultsMIC values against polymyxin B were ≥ 4 μg/mL for 44 of the strains and were 2 μg/mL for the other 6 strains. MICs against polymyxin B in the isolates tested were significantly reduced by the addition of resveratrol. The degree of decline depended on the bacteria, ranging from 1/2 MIC to 1/512 MIC, and the higher the concentration of resveratrol, the greater the decrease. Checkerboard analysis indicated a synergistic effect between resveratrol and polymyxin B; the optimal drug concentration for different bacteria was different, that of resveratrol ranging from 32 μg/mL to 128 μg/mL. Subsequent time-kill experiments showed that a combination of polymyxin B and resveratrol was more effective in killing bacteria.ConclusionsOur in vitro studies have shown that resveratrol can increase the sensitivity of MDR bacterial strains to polymyxin B, suggesting a potential new approach to the treatment of MDR infections.

Highlights

Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments
We selected 50 multi-drug resistant strains (26 strains of K. pneumoniae and 24 strains of E. coli) for analysis (Table 1); six strains were sensitive to polymyxin B, and 44 strains were resistant
Resistance to polymyxin B in E. coli was due to the mcr-1 gene, while only one strain of resistant

Summary

Introduction

Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. We selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect. The emergence of Gram-negative bacteria that are resistant to multiple antibiotics has put a lot of pressure on healthcare centers around the world [1]. Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Full list of author information is available at the end of the article infections caused by susceptible Gram-negative bacteria [3]. Polymyxin B interacts directly with the lipid A component of lipopolysaccharide, thereby increasing the permeability of bacterial cell membranes

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Discussion

Conclusion