Bacterial infections in humans and animals caused by multidrug-resistant (MDR) pathogens pose a serious threat to public health. New antibacterial targets are extremely urgent to solve the dilemma of cross-resistance. Phospholipids are critical components in bacterial envelopes and involve diverse crucial processes to maintain homeostasis and modulate metabolism. Targeting phospholipids and their synthesis pathways has been largely overlooked because conventional membrane-targeted substances are non-specific with cytotoxicity. In this review, we first introduce the structure and physiological function of phospholipids in bacteria. Subsequently, we describe the chemical diversity of novel ligands targeting phospholipids, structure-activity relationships (SAR), modes of action (MOA), and pharmacological effects. Finally, we prospect the advantage of bacterial phospholipids as promising antibacterial targets. In conclusion, these findings will shed light on discovering and developing new antibacterial drugs to combat MDR bacteria-associated infections.

中文翻译：

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靶向细菌磷脂及其合成途径，用于抗生素发现


由多重耐药 （MDR） 病原体引起的人类和动物细菌感染对公共卫生构成严重威胁。新的抗菌靶点解决交叉耐药困境极为迫切。磷脂是细菌包膜中的关键成分，涉及维持体内平衡和调节新陈代谢的不同关键过程。靶向磷脂及其合成途径在很大程度上被忽视了，因为传统的膜靶向物质是非特异性的，具有细胞毒性。在本文中，我们首先介绍了磷脂在细菌中的结构和生理功能。随后，我们描述了靶向磷脂的新型配体的化学多样性、构效关系 （SAR）、作用方式 （MOA） 和药理作用。最后，我们展望了细菌磷脂作为有前途的抗菌靶点的优势。总之，这些发现将为发现和开发新的抗菌药物来对抗 MDR 细菌相关感染提供指导。