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Abstract Title:

Phloretin potentiates polymyxin E activity against gram-negative bacteria.

Abstract Source:

Life Sci. 2021 Dec 15 ;287:120085. Epub 2021 Oct 23. PMID: 34699905

Abstract Author(s):

Runbao Du, Qianghua Lv, Wei Hu, Xiaoning Hou, Yonglin Zhou, Xuming Deng, Liping Sun, Li Li, Yanhong Deng, Jianfeng Wang

Article Affiliation:

Runbao Du

Abstract:

AIMS: The spread of plasmid-mediated polymyxin resistance has jeopardized the use of polymyxin, the last defender that combats infections caused by multidrug-resistant (MDR) gram-negative pathogens.

MAIN METHODS: In this study, phloretin, as a monomeric compound extracted from natural plants, showed a good synergistic effect with polymyxin E against gram-negative bacteria, as evaluated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and Western blot assays. A model of mice infected by Salmonella sp. stain HYM2 was established to further identify the synergistic effect of phloretin with polymyxin E.

KEY FINDINGS: The results suggested that phloretin had the potential ability to recover the antibacterial sensitivity of polymyxin E from 64 μg/mL to no more than 2 μg/mL in E. coli ZJ478 or in Salmonella sp. stain HYM2 with a 32-fold decrease. A series of strains, including mcr-1-positive and mcr-1-negative strains, were treated with a combination of phloretin and polymyxin E, and the fractional inhibitory concentration (FIC) values were all found to be below 0.5. However, the combination of phloretin and polymyxin E did not lead to bacterial resistance. In vivo, the survival rate of infected mice reached nearly 80% with the combination treatment, and the cecal colony value also decreased significantly.

SIGNIFICANCE: All the above results indicated that phloretin is a potential polymyxin potentiator to combat gram-negative stains.

Study Type : Animal Study

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