Gunn J S, Lim K B, Krueger J, Kim K, Guo L, Hackett M, Miller S I
University of Washington, Department of Medicine, Seattle 98195, USA.
Mol Microbiol. 1998 Mar;27(6):1171-82. doi: 10.1046/j.1365-2958.1998.00757.x.
Antimicrobial peptides are distributed throughout the animal kingdom and are a key component of innate immunity. Salmonella typhimurium regulates mechanisms of resistance to cationic antimicrobial peptides through the two-component systems PhoP-PhoQ and PmrA-PmrB. Polymyxin resistance is encoded by the PmrA-PmrB regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A. Two PmrA-PmrB-regulated S. typhimurium loci (pmrE and pmrF) have been identified that are necessary for resistance to polymyxin and for the addition of aminoarabinose to lipid A. One locus, pmrE, contains a single gene previously identified as pagA (or ugd) that is predicted to encode a UDP-glucose dehydrogenase. The second locus, pmrF, is the second gene of a putative operon predicted to encode seven proteins, some with similarity to glycosyltransferases and other complex carbohydrate biosynthetic enzymes. Genes immediately flanking this putative operon are also regulated by PmrA-PmrB and/or have been associated with S. typhimurium polymyxin resistance. This work represents the first identification of non-regulatory genes necessary for modification of lipid A and subsequent antimicrobial peptide resistance, and provides support for the hypothesis that lipid A aminoarabinose modification promotes resistance to cationic antimicrobial peptides.
抗菌肽分布于整个动物界，是天然免疫的关键组成部分。鼠伤寒沙门氏菌通过双组分系统PhoP - PhoQ和PmrA - PmrB来调控对阳离子抗菌肽的抗性机制。多粘菌素抗性由PmrA - PmrB调控子编码，其产物用乙醇胺修饰脂多糖（LPS）核心和脂质A区域，并将氨基阿拉伯糖添加到脂质A的4'磷酸上。已鉴定出两个受PmrA - PmrB调控的鼠伤寒沙门氏菌基因座（pmrE和pmrF），它们对于多粘菌素抗性以及向脂质A添加氨基阿拉伯糖是必需的。一个基因座pmrE包含一个先前被鉴定为pagA（或ugd）的单一基因，预计该基因编码一种UDP - 葡萄糖脱氢酶。第二个基因座pmrF是一个推定操纵子的第二个基因，预计该操纵子编码七种蛋白质，其中一些与糖基转移酶和其他复杂碳水化合物生物合成酶具有相似性。紧邻这个推定操纵子的基因也受PmrA - PmrB调控和/或与鼠伤寒沙门氏菌多粘菌素抗性相关。这项工作首次鉴定了脂质A修饰及随后的抗菌肽抗性所必需的非调控基因，并为脂质A氨基阿拉伯糖修饰促进对阳离子抗菌肽抗性的假说提供了支持。
