Phospholipid Diversity and Biosynthesis Pathway in Bacteria: Potential Antibacterial Targets

Bacterial infections have posed a serious threat globally. The discovery of new targets and the development of novel antimicrobial agents are urgently needed to combat these bacterial infections. The bacterial membrane is a dynamic and essential structure that not only fortifies cellular integrity but also maintains bacterial core metabolism and environmental adaptation. Phospholipids constitute the primary building blocks of the bacterial membrane. The structural variability of phospholipids in both their head groups and acyl chains enables them to dynamically adjust the membrane's biophysical characteristics such as fluidity, curvature and surface charge, thereby directly shaping membrane functionality. In bacteria, these chemo-diverse phospholipids are tightly controlled by their conserved biosynthetic pathways. In this review, we summarize the structural diversity of bacterial phospholipids and their physicochemical implications, describe the biosynthesis and modification mechanisms, and discuss the critical roles of phospholipid diversity in bacterial stress adaptation and antibiotic resistance. Moreover, we highlight emerging antimicrobial strategies that directly target bacterial phospholipids or inhibit key enzymes in phospholipid biosynthetic pathways. These findings will shed light on the discovery of antibacterial targets to develop novel antibacterial agents.