金黄色葡萄球菌细胞膜磷脂合成的研究进展

Research progress in the synthesis of cell membrane phospholipids in Staphylococcus aureus

摘要:

金黄色葡萄球菌引起的危害是目前我国微生物安全的重要问题之一。金黄色葡萄球菌通过脂肪酸生物合成磷脂酸(磷脂合成必需中间体)合成细胞膜磷脂以完成自身繁殖。因此，抑制菌体磷脂酸合成可有效防控金黄色葡萄球菌对环境及生物体造成危害。然而，金黄色葡萄球菌可经II型脂肪酸合成(type II fatty acid synthesis, FASII)通路和旁路两条途径合成磷脂酸，常规抑菌剂仅靶向抑制FASII通路，可能导致菌体在富含外源脂肪酸条件下出现“旁路逃逸”，形成防控漏洞。为此，本文系统总结金黄色葡萄球菌基于FASII通路和旁路合成细胞磷脂酸及磷脂酸向其他磷脂类物质转化的信号传导过程，讨论抑菌物质靶向抑制上述信号传导过程中可能的关键靶点，为新型抑菌剂开发提供理论指导。

关键词:金黄色葡萄球菌;II型脂肪酸生物合成(FASII)通路;II型脂肪酸生物合成(FASII)旁路;抑菌靶点;新型抑菌剂

Abstract:

Staphylococcus aureus is a major contributor to the microbiological safety hazards in China. It uses fatty acids to synthesize phosphatidic acid (an essential intermediate in the synthesis of cell membrane phospholipids) for reproduction. Therefore, inhibiting the synthesis of phosphatidic acid can effectively control S. aureus and thus reduce the damage to the environment and organisms. However, S. aureus has the ability to synthesize phosphatidic acid via both the type II fatty acid synthesis (FASII) pathway and the FASII bypass. The common inhibitors against S. aureus only target the FASII pathway, which can result in the emergence of FASII bypass escape when the bacteria are exposed to high levels of exogenous fatty acids, creating a potential gap in the protection. This paper provides a comprehensive overview of the signaling processes of the FASII pathway and bypass for synthesizing phospholipid acid, as well as the conversion of phospholipid acid to other phospholipids in S. aureus. Furthermore, the key targets of the signaling processes that may be inhibited by antibacterial agents are discussed. This review may provide theoretical guidance for the development of new bacterial inhibitors.

Key words:Staphylococcus aureus;type II fatty acid synthesis (FASII) pathway;type II fatty acid synthesis (FASII) bypass;antibacterial targets;new bacterial inhibitors