Equisetin Restores Colistin Sensitivity against Multi-Drug Resistant Gram-Negative Bacteria
The overuse of antibiotics and the scarcity of new drugs have led to a serious antimicrobial resistance crisis, especially for multi-drug resistant (MDR) Gram-negative bacteria. In the present study, we investigated the antimicrobial activity of a marine antibiotic equisetin in combination with coli...
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| Main Authors: | , , , , |
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| Format: | Book |
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MDPI AG,
2021-10-01T00:00:00Z.
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| Summary: | The overuse of antibiotics and the scarcity of new drugs have led to a serious antimicrobial resistance crisis, especially for multi-drug resistant (MDR) Gram-negative bacteria. In the present study, we investigated the antimicrobial activity of a marine antibiotic equisetin in combination with colistin against Gram-negative bacteria and explored the mechanisms of synergistic activity. We tested the synergistic effect of equisetin in combination with colistin on 23 clinical <i>mcr-1</i> positive isolates and found that 4 µg/mL equisetin combined with 1 µg/mL colistin showed 100% inhibition. Consistently, equisetin restored the sensitivity of 10 species of <i>mcr-1</i> positive Gram-negative bacteria to colistin. The combination of equisetin and colistin quickly killed 99.9% bacteria in one hour in time-kill assays. We found that colistin promoted intracellular accumulation of equisetin in colistin-resistant <i>E. coli</i> based on LC-MS/MS analysis. Interestingly, equisetin boosted ROS accumulation in <i>E. coli</i> in the presence of colistin. Moreover, we found that equisetin and colistin lost the synergistic effect in two LPS-deficient <i>A. baumannii</i> strains. These findings suggest that colistin destroys the hydrophobic barrier of Gram-negative bacteria, facilitating equisetin to enter the cell and exert its antibacterial effect. Lastly, equisetin restored the activity of colistin in a <i>G. mellonella</i> larvae infection model. Collectively, these results reveal that equisetin can potentiate colistin activity against MDR Gram-negative bacteria including colistin-resistant strains, providing an alternative approach to address Gram-negative pathogens associated with infections in clinics. |
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| Item Description: | 10.3390/antibiotics10101263 2079-6382 |