Inhibition of AcrAB-TolC enhances antimicrobial activity of phytochemicals in Pectobacterium brasiliense

Frontiers in Plant Science

Plant Science

Hanoch Senderowitz¹  Netaly Khazanov¹  Iris Yedidia²  Ortal Galsurker²  Manoj Pun³  Zohar Kerem⁴ 

[1] Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel;The Institute of Plant Sciences, Volcani Center, Agricultural Research Organization (ARO), Rishon Lezion, Israel;The Institute of Plant Sciences, Volcani Center, Agricultural Research Organization (ARO), Rishon Lezion, Israel;The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel;The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel;

关键词: AcrAB-TolC;    efflux pumps;    inhibitors;    naringenin;    Pectobacterium brasiliense;    phloretin;    virulence;    PAβN;   

DOI  :  10.3389/fpls.2023.1161702

 received in 2023-02-08, accepted in 2023-04-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe eons-long co-evolvement of plants and bacteria led to a plethora of interactions between the two kingdoms, in which bacterial pathogenicity is counteracted by plant-derived antimicrobial defense molecules. In return, efflux pumps (EP) form part of the resistance mechanism employed by bacteria to permit their survival in this hostile chemical environment. In this work we study the effect of combinations of efflux pump inhibitors (EPIs) and plant-derived phytochemicals on bacterial activity using Pectobacteriun brasiliense 1692 (Pb1692) as a model system.MethodsWe measured the minimal inhibitory concentration (MIC) of two phytochemicals, phloretin (Pht) and naringenin (Nar), and of one common antibiotic ciprofloxacin (Cip), either alone or in combinations with two known inhibitors of the AcrB EP of Escherichia coli, a close homolog of the AcrAB-TolC EP of Pb1692. In addition, we also measured the expression of genes encoding for the EP, under similar conditions.ResultsUsing the FICI equation, we observed synergism between the EPIs and the phytochemicals, but not between the EPIs and the antibiotic, suggesting that EP inhibition potentiated the antimicrobial activity of the plant derived compounds, but not of Cip. Docking simulations were successfully used to rationalize these experimental results.DiscussionOur findings suggest that AcrAB-TolC plays an important role in survival and fitness of Pb1692 in the plant environment and that its inhibition is a viable strategy for controlling bacterial pathogenicity.

【 授权许可】

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Copyright © 2023 Pun, Khazanov, Galsurker, Kerem, Senderowitz and Yedidia