Biological roles of the O-methyl phosphoramidate capsule modification in Campylobacter jejuni.

Biological roles of the O-methyl phosphoramidate capsule modification in Campylobacter jejuni.
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O-甲基氨基磷酸酯胶囊修饰在空肠弯曲杆菌中的生物学作用。

DOI:
10.1371/journal.pone.0087051
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Szymanski CM
Szymanski CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
van Alphen LB;Wenzel CQ;Richards MR;Fodor C;Ashmus RA;Stahl M;Karlyshev AV;Wren BW;Stintzi A;Miller WG;Lowary TL;Szymanski CM

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空肠弯曲菌是世界范围内细菌性胃肠炎的主要原因,这种微生物的荚膜多糖(CPS)是维持和疾病所必需的。空肠弯曲菌产生超过47种不同的衣壳结构,包括一种独特的O-甲基磷酰胺(MeOPN)修饰,存在于大多数空肠弯曲菌分离株上。虽然MeOPN结构在自然界中很少见,但它在结构上与一些合成农药有相似之处。在这项研究中,我们通过全基因组比较和高分辨率魔角旋转核磁共振证明,MeOPN修饰在几个弯曲杆菌物种中是常见的。利用空肠弯曲菌81-176产生的MeOPN生物合成和转移酶突变,我们观察到MeOPN从细胞表面的丢失与Caco-2上皮细胞侵袭力的增加和对人血清杀伤能力的降低有关。在空肠弯曲菌中,观察到的血清介导的杀伤主要是由经典补体途径的激活引起的。空肠弯曲菌MeOPN转移酶突变株在鸡体内的定殖率与野生型相似,但与野生型混合感染时,在仔猪中的定殖率下降了5倍。在斑纹夜蛾幼虫中,MeOPN转移酶突变体能够在野生型水平上杀死这些昆虫。此外,向幼虫注射MeOPN连接的单糖或从野生型菌株中纯化的CPS并未导致幼虫死亡,表明MeOPN没有固有的杀虫活性。
Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS) of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN) modification present on most C. jejuni isolates. Although the MeOPN structure is rare in nature it has structural similarity to some synthetic pesticides. In this study, we have demonstrated, by whole genome comparisons and high resolution magic angle spinning NMR, that MeOPN modifications are common to several Campylobacter species. Using MeOPN biosynthesis and transferase mutants generated in C. jejuni strain 81–176, we observed that loss of MeOPN from the cell surface correlated with increased invasion of Caco-2 epithelial cells and reduced resistance to killing by human serum. In C. jejuni, the observed serum mediated killing was determined to result primarily from activation of the classical complement pathway. The C. jejuni MeOPN transferase mutant showed similar levels of colonization relative to the wild-type in chickens, but showed a five-fold drop in colonization when co-infected with the wild-type in piglets. In Galleria mellonella waxmoth larvae, the MeOPN transferase mutant was able to kill the insects at wild-type levels. Furthermore, injection of the larvae with MeOPN-linked monosaccharides or CPS purified from the wild-type strain did not result in larval killing, indicating that MeOPN does not have inherent insecticidal activity.
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发表时间: 1985-01-01
影响因子: 6.4
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