Pun Manoj, Khazanov Netaly, Galsurker Ortal, Kerem Zohar, Senderowitz Hanoch, Yedidia Iris
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.
Front Plant Sci. 2023 May 9;14:1161702. doi: 10.3389/fpls.2023.1161702. eCollection 2023.
The 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 1692 (Pb1692) as a model system.
We 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 , 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.
Using 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.
Our 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.
植物和细菌历经漫长的共同进化，导致了这两个王国之间大量的相互作用，其中植物衍生的抗菌防御分子可对抗细菌致病性。作为回报，外排泵（EP）构成了细菌在这种恶劣化学环境中生存所采用的抗性机制的一部分。在这项工作中，我们以1692（Pb1692）为模型系统，研究外排泵抑制剂（EPI）与植物衍生的植物化学物质组合对细菌活性的影响。
我们测量了两种植物化学物质根皮素（Pht）和柚皮素（Nar）以及一种常用抗生素环丙沙星（Cip）单独使用或与两种已知的AcrB EP抑制剂联合使用时的最小抑菌浓度（MIC），该抑制剂是Pb1692的AcrAB - TolC EP的密切同源物。此外，我们还在类似条件下测量了编码EP的基因的表达。
使用FICI方程，我们观察到EPI与植物化学物质之间存在协同作用，但EPI与抗生素之间没有协同作用，这表明抑制EP可增强植物衍生化合物的抗菌活性，但不能增强Cip的抗菌活性。对接模拟成功用于合理解释这些实验结果。
我们的研究结果表明，AcrAB - TolC在Pb1692在植物环境中的生存和适应性中起重要作用，并且抑制它是控制细菌致病性的可行策略。
