PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance
PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance
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DOI：
10.1046/j.1365-2958.1998.00757.x
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发表时间：
1998-03-01
影响因子：
3.6
通讯作者：
Miller, SI
中科院分区：
文献类型：
--
作者：
Gunn, JS;Lim, KB;Miller, SI
抗菌肽广泛分布于整个动物界，是天然免疫的重要组成部分。鼠伤寒沙门氏菌通过Phop-PhoQ和PmrA-pmrB两个系统调节对阳离子抗菌肽的抗性机制。多粘菌素抗性是由PmrA-pmrB调节子编码的，其产物用乙醇胺修饰脂多糖(LPS)核心和脂类A区域，并在脂类A的4‘磷酸盐上添加氨基阿拉伯糖。已鉴定出两个由PmrA-pmrB调控的鼠伤寒沙门氏菌座位(pmrE和PMRF)，它们是对多粘菌素的抗性所必需的，也是将氨基阿拉伯糖加到脂类A中所必需的。一个基因座pmrE包含一个先前被确定为PagA(或ugD)的单一基因，该基因被预测编码UDP-葡萄糖脱氢酶。第二个基因，PMRF，是一个可能的操纵子的第二个基因，预计编码七种蛋白质，其中一些与糖基转移酶和其他复杂的碳水化合物生物合成酶相似。紧邻这个假定操纵子两侧的基因也受PmrA-pmrB调控和/或与鼠伤寒沙门氏菌多粘菌素抗性有关。这项工作代表了首次鉴定了修饰A类脂蛋白和随后的抗菌肽耐药性所必需的非调控基因，并支持了A类氨基阿拉伯糖修饰促进阳离子抗菌肽耐药性的假说。
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.