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Phloretin potentiates polymyxin E activity against gram-negative bacteria
Runbao Du1, Qianghua Lv1, Wei Hu1
1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Life Sciences
|October 26, 2021
Summary
Phloretin, a natural compound, restores polymyxin E effectiveness against multidrug-resistant gram-negative bacteria. This combination therapy shows promise in reducing infections and increasing survival rates in mice.
Area of Science:
- Microbiology and Infectious Diseases
- Pharmacology and Drug Discovery
- Natural Product Chemistry
Background:
- The rise of plasmid-mediated polymyxin resistance in multidrug-resistant (MDR) gram-negative pathogens poses a significant threat to public health.
- Polymyxins are critical last-resort antibiotics for treating infections caused by these challenging pathogens.
- The emergence of resistance necessitates the development of novel strategies to restore the efficacy of existing antibiotics.
Purpose of the Study:
- To investigate the potential synergistic effect of phloretin, a natural plant-derived compound, with polymyxin E against gram-negative bacteria.
- To evaluate the ability of phloretin to overcome polymyxin resistance in various gram-negative strains.
- To assess the in vivo efficacy and safety of the phloretin-polymyxin E combination therapy.
Main Methods:
- Minimal inhibitory concentration (MIC) assays were performed to determine the synergistic effect of phloretin and polymyxin E.
- Growth curve, time-killing assays, and Western blot analyses were conducted to elucidate the mechanism of action.
- An in vivo mouse model infected with Salmonella sp. strain HYM2 was used to evaluate therapeutic efficacy.
Main Results:
- Phloretin significantly reduced the MIC of polymyxin E against resistant strains (e.g., E. coli ZJ478, Salmonella sp. HYM2) by up to 32-fold.
- Fractional inhibitory concentration (FIC) index values for the combination were consistently below 0.5, indicating synergy.
- The combination therapy did not induce bacterial resistance and demonstrated improved survival rates (nearly 80%) and reduced bacterial load in infected mice.
Conclusions:
- Phloretin acts as a potent potentiator of polymyxin E, effectively restoring sensitivity in resistant gram-negative bacteria.
- The combination of phloretin and polymyxin E presents a promising therapeutic strategy against MDR gram-negative infections.
- Phloretin's natural origin and synergistic activity make it a valuable candidate for combating antibiotic resistance.
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