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由于新抗菌药物的不断发现,80年代曾一度认为细菌感染性疾病已经控制,美国、日本等国一些制药单位已开始减少寻找新抗菌药物,而转向寻找抗真菌与抗病毒药物。但在90年代,耐药菌特别是多重耐药菌株日益增多,且向全球许多地区蔓延,新抗菌药物的寻找又提上日程。可是大多所谓抗菌新药仅是旧药的改良,作用机制不变。类脂A是革兰阴性菌外膜脂多糖(LPS)的重要结构。LPS起到屏障的作用,阻碍物质经外膜的通透性。类脂A的遗传缺陷或阳离子肽的损伤可影响LPS的完整性,加强细菌对补体杀菌作用的敏感性。研究认为类脂A-KDO(2-酮基-3-脱氧辛酸)是革兰阴性菌生存的必要物质,其合成的突变可引起细菌死亡。近年来令人注意的是发现了一种新药称L-573,655,是一种氧肟酸。当浓度在100μg/ml时,可抑制80%～90%LPS的合成,也影响DNA、RNA、蛋白质与磷脂的合成。大肠杆菌的类脂A合成途径中有9种酶,脱乙酰
Due to the continuous discovery of new antibacterial drugs, bacterial infections were once thought to have been controlled in the 1980s. Some pharmaceutical companies in the United States, Japan and other countries have started to reduce their search for new antimicrobial agents and turned to antifungal and antiviral drugs. However, in the 1990s, the number of multidrug-resistant bacteria, especially multi-drug resistant strains, has been increasing and spreading to many parts of the world. The search for new antimicrobial agents has been put on the agenda. However, most of the so-called antibacterial drugs only improve the old drugs, the same mechanism of action. Lipid A is an important structure of gram-negative bacteria outer membrane lipopolysaccharide (LPS). LPS acts as a barrier, hindering the permeability of substances through the outer membrane. Genetic defects of lipid A or damage of cationic peptides can affect the integrity of LPS and enhance the sensitivity of bacteria to the bactericidal effect of complement. Lipid A-KDO (2-keto-3-deoxyoctanoic acid) is considered to be an essential substance for the survival of Gram-negative bacteria, and its synthetic mutation can cause bacterial death. What has drawn attention in recent years is the discovery of a new drug called L-573,655, a hydroxamic acid. When the concentration is 100μg / ml, can inhibit 80% ~ 90% LPS synthesis, but also affect DNA, RNA, protein and phospholipid synthesis. There are 9 enzymes in the lipid A synthesis pathway of Escherichia coli which are deacetylated