Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with
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RESEARCH ARTICLE
Open Access
Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance Li Liu1†, Jingyi Yu1†, Xiaofei Shen2, Xingwei Cao3, Qing Zhan4, Yinjuan Guo5,6 and Fangyou Yu5,6*
Abstract Background: Multidrug 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. Results: MIC 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. Conclusions: Our 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. Keywords: Polymyxin B, Resveratrol, Combination therapy, Multidrug resistance (MDR)
Background In recent years, 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]. Infections caused by multidrug-resistant (MDR) Gram-negative bacteria not only have a higher mortality rate [2], but also impose greater economic burdens than * Correspondence: [email protected] † Li Liu and Jingyi Yu contributed equally to this work. 5 Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, China 6 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, China Full list of author information is available at the end of the article
infections caused by susceptible Gram-negative bacteria [3]. New antibiotics or more effective therapies are therefore urgently needed to solve this problem. In many situations, colistin and polymyxin B are considered the last antibiotics of choice [4]. Polymixin B has high affinity for the lipopolysaccharides (LPS) of Gram-negative bacilli and has been re-applied in the clinic. Polymixin B induces LPS aggregation, increasing the charge on cell membrane surfaces, and making it internalize and bind to the cell membrane, resulting in the leakage of cell contents [5]. Polymyxin B interacts directly with the lipid A
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