The genetic bases for the variation in the lipo-oligosaccharide of the mucosal pathogen, Campylobacter jejuni -: Biosynthesis of sialylated ganglioside mimics in the core oligosaccharide

The genetic bases for the variation in the lipo-oligosaccharide of the mucosal pathogen, Campylobacter jejuni -: Biosynthesis of sialylated ganglioside mimics in the core oligosaccharide
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DOI:
10.1074/jbc.m108452200
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发表时间:
2002-01-04
影响因子:
4.8
通讯作者:
Wakarchuk, WW
Wakarchuk, WW
中科院分区:
生物学2区
文献类型:
--
作者:
Gilbert, M;Karwaski, MF;Wakarchuk, WW

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我们比较了11个空肠弯曲菌菌株的脂寡糖(LOS)生物合成位点,这些菌株在LOS外核中表达了总共8种不同的神经节苷脂模拟物。根据基因的组织,11个相应的位点可以分为三类,其中一类显然是其他两个之间的中间进化步骤。比较基因组学和特定糖基转移酶的表达结合体外活性测定,使我们能够确定至少五种不同的机制,使C。jejuni以如下改变LOS外核的结构:1)不同的基因互补物; 2)由于均聚体束的相位变化; 3)通过缺失或插入单个碱基(没有相位变化)的基因失活; 4)导致糖基转移酶失活的单突变;和5)导致具有不同受体特异性的“等位”糖基转移酶的单或多突变。11 C表示的LOS外核结构的差异。所检查的空肠菌株可以通过本工作中描述的五种机制中的一种或多种来解释。
We have compared the lipo-oligosaccharide (LOS) biosynthesis loci from 11 Campylobacter jejuni strains expressing a total of 8 different ganglioside mimics in their LOS outer cores. Based on the organization of the genes, the 11 corresponding loci could be classified into three classes, with one of them being clearly an intermediate evolutionary step between the other two. Comparative genomics and expression of specific glycosyltransferases combined with in vitro activity assays allowed us to identify at least five distinct mechanisms that allow C. jejuni to vary the structure of the LOS outer core as follows: 1) different gene complements; 2) phase variation because of homopolymeric tracts; 3) gene inactivation by the deletion or insertion of a single base (without phase variation); 4) single mutation leading to the inactivation of a glycosyltransferase; and 5) single or multiple mutations leading to "allelic" glycosyltransferases with different acceptor specificities. The differences in the LOS outer core structures expressed by the 11 C. jejuni strains examined can be explained by one or more of the five mechanisms described in this work.