Membranes─cells’ essential scaffolds─are valid molecular targets for substances with an antimicrobial effect. While certain substances, such as octenidine, have been developed to target membranes for antimicrobial purposes, the recently reported molecule, fabimycin (F2B)─a novel agent targeting drug-resistant Gram-negative bacteria─has not received adequate attention regarding its activity on membranes in the literature. The following study aims to investigate the effects of F2B on different bacterial membrane models, including simple planar bilayers and more complex bilayer systems that mimic the Escherichia coli shell equipped with double inner and outer bilayers. Our results show that F2B exhibited more pronounced interactions with bacterial membrane systems compared to the control PC system. Furthermore, we observed significant changes in local membrane property homeostasis in both the inner and outer membrane models, specifically in the case of lateral diffusion, membrane thickness, and membrane resilience (compressibility, tilt). Finally, our results showed that the effect of F2B differed in a complex system and a single membrane system. Our study provides new insights into the multifaceted activity of F2B, demonstrating its potential to disrupt bacterial membrane homeostasis, indicating that its activity extends the currently known mechanism of FabI enzyme inhibition. This disruption, coupled with the ability of F2B to penetrate the outer membrane layers, sheds new light on the behavior of this antimicrobial molecule. This highlights the importance of the interaction with the membrane, crucial in combating bacterial infections, particularly those caused by drug-resistant strains.

中文翻译：

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法比霉素的多方面活性：细菌膜模型分子动力学研究的见解


膜——细胞的重要支架——是具有抗菌作用的物质的有效分子靶标。虽然奥替尼啶等某些物质已被开发用于靶向膜以达到抗菌目的，但最近报道的分子法比霉素 (F2B)（一种针对耐药革兰氏阴性菌的新型药物）对其膜上的活性尚未得到足够的关注在文献中。以下研究旨在研究 F2B 对不同细菌膜模型的影响，包括简单的平面双层和更复杂的双层系统，这些双层系统模仿配备有双层内外双层的大肠杆菌外壳。我们的结果表明，与对照 PC 系统相比，F2B 与细菌膜系统表现出更明显的相互作用。此外，我们观察到内膜和外膜模型中局部膜特性稳态的显着变化，特别是在横向扩散、膜厚度和膜弹性（可压缩性、倾斜）的情况下。最后，我们的结果表明，F2B 的效果在复杂系统和单膜系统中不同。我们的研究为 F2B 的多方面活性提供了新的见解，证明了其破坏细菌膜稳态的潜力，表明其活性扩展了目前已知的 FabI 酶抑制机制。这种破坏，加上 F2B 穿透外膜层的能力，为了解这种抗菌分子的行为提供了新的线索。这凸显了与膜相互作用的重要性，这对于对抗细菌感染至关重要，尤其是由耐药菌株引起的细菌感染。