Mode of action of membrane-targeting antimicrobial compounds

多年来，膜靶向抗菌剂(MTA)已成功应用于医学领域。这些抗菌剂可能延缓甚至消除敏感病原体的耐药性发展，这是有理论原因的。然而，令人惊讶的是，MTA对有害植物和食品微生物的使用仍然非常有限。假定MTA有一种微生物难以克服的行动模式，因此可以提供有效的、最重要的是持久的控制方法。由于缺乏关于MTA作用模式的基本知识，这无疑阻碍了这些类型抗菌剂的有效使用。 这项研究计划的长期目标是阐明MTA在成功应用这些化合物控制有害植物和食品微生物方面的确切作用模式。目前的研究方案使用新的方法在分子、细胞和生化水平上研究特定MTA类别(脂肽)的作用机制。更确切地说，将通过全内反射荧光(TIRFM)、原子力(AFM)和电子显微镜(EM)等技术，结合生物分析和生物物理化学以及生物化学技术来研究MTA在增加膜流动性、膜孔形成以及与膜组件结合/相互作用方面的作用。 因此，该计划将揭示这些膜靶向化合物的确切作用模式，并为它们作为对抗有害植物和食品微生物的合成化学品的新型、高效和持久替代品的发展提供洞察力。

Membrane-targeting antimicrobials (MTAs) have been employed successfully in medicine for a number of years. There are theoretical reasons why these antimicrobials might delay or even eliminate resistance development in sensitive pathogens. Yet surprisingly, use of MTAs against harmful plant and food microorganisms is still very limited. It is hypothesized that MTAs have a mode of action that is difficult for microorganisms to overcome and could therefore provide efficient and, most importantly, durable methods of control. The lack of fundamental knowledge on the mode of action of MTAs has most definitely hampered the efficient use of these types of antimicrobials. The long term goal of this research program aims to elucidate the precise mode of action of MTAs for successful application of these compounds toward the control of harmful plant and food microorganisms. The present research proposal uses novel approaches to investigate the mechanisms of action of a specific MTA class (lipopeptides) at the molecular, cellular, and biochemical level. More precisely, the role of MTAs in increased membrane fluidity, membrane pore formation, and binding/interacting with membrane components will be studied through techniques such as total internal reflection fluorescence (TIRFM), atomic force (AFM) and electron (EM) microscopy, concurrently with techniques in bio-analytical and biophysical chemistry as well as biochemistry. This program will therefore shed light into the precise mode of action of these membrane-targeting compounds and provide insight into their development as novel, efficient, and long-lasting alternatives to synthetic chemicals against harmful plant and food microorganisms.