Panda Gayatree, Dash Sabyasachi, Sahu Santosh Kumar
Department of Biotechnology, Maharaja Sriram Chandra Bhanjadeo University (Erstwhile: North Orissa University), Baripada 757003, India.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Membranes (Basel). 2022 Sep 22;12(10):914. doi: 10.3390/membranes12100914.
Membrane-targeted molecules such as cationic antimicrobial peptides (CAMPs) are amongst the most advanced group of antibiotics used against drug-resistant bacteria due to their conserved and accessible targets. However, multi-drug-resistant bacteria alter their plasma membrane (PM) lipids, such as lipopolysaccharides (LPS) and phospholipids (PLs), to evade membrane-targeted antibiotics. Investigations reveal that in addition to LPS, the varying composition and spatiotemporal organization of PLs in the bacterial PM are currently being explored as novel drug targets. Additionally, PM proteins such as Mla complex, MPRF, Lpts, lipid II flippase, PL synthases, and PL flippases that maintain PM integrity are the most sought-after targets for development of new-generation drugs. However, most of their structural details and mechanism of action remains elusive. Exploration of the role of bacterial membrane lipidome and proteome in addition to their organization is the key to developing novel membrane-targeted antibiotics. In addition, membranotropic phytochemicals and their synthetic derivatives have gained attractiveness as popular herbal alternatives against bacterial multi-drug resistance. This review provides the current understanding on the role of bacterial PM components on multidrug resistance and their targeting with membranotropic phytochemicals.
诸如阳离子抗菌肽（CAMP）之类的膜靶向分子是用于对抗耐药细菌的最先进的抗生素类别之一，因为它们具有保守且易于接近的靶点。然而，多重耐药细菌会改变其质膜（PM）脂质，如脂多糖（LPS）和磷脂（PL），以逃避膜靶向抗生素。研究表明，除了LPS之外，细菌质膜中PL的不同组成和时空组织目前也正在作为新的药物靶点进行探索。此外，维持质膜完整性的质膜蛋白，如Mla复合物、MPRF、Lpts、脂质II翻转酶、PL合成酶和PL翻转酶，是开发新一代药物最受追捧的靶点。然而，它们的大多数结构细节和作用机制仍然难以捉摸。除了细菌膜脂质组和蛋白质组的组织之外，探索它们的作用是开发新型膜靶向抗生素的关键。此外，膜otropic植物化学物质及其合成衍生物作为对抗细菌多重耐药性的流行草药替代品也受到了关注。本综述提供了对细菌质膜成分在多重耐药性中的作用及其与膜otropic植物化学物质靶向作用的当前理解。
