Poly Frédéric, Read Timothy D, Chen Yu-Han, Monteiro Mario A, Serichantalergs Oralak, Pootong Piyarat, Bodhidatta Ladaporn, Mason Carl J, Rockabrand David, Baqar Shahida, Porter Chad K, Tribble David, Darsley Michael, Guerry Patricia
Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Infect Immun. 2008 Dec;76(12):5655-67. doi: 10.1128/IAI.00780-08. Epub 2008 Sep 22.
The development of vaccines against Campylobacter jejuni would be facilitated by the ability to perform phase II challenge studies. However, molecular mimicry of the lipooligosaccharide (LOS) of most C. jejuni strains with human gangliosides presents safety concerns about the development of Guillain-Barré syndrome. Clinical isolates of C. jejuni that appeared to lack genes for the synthesis of ganglioside mimics were identified by DNA probe analyses. Two clinical isolates from Southeast Asia (strains BH-01-0142 and CG8421) were determined to express the LOS type containing N-acetyl quinovosamine. No ganglioside structures were observed to be present in the LOSs of these strains, and pyrosequence analyses of the genomes of both strains confirmed the absence of genes involved in ganglioside mimicry. The capsule polysaccharide (CPS) of BH-01-0142 was determined to be composed of galactose (Gal), 6-deoxy-ido-heptose, and, in smaller amounts, D-glycero-D-ido-heptose, and the CPS of CG8421 was observed to contain Gal, 6-deoxy-altro-heptose, N-acetyl-glucosamine, and minor amounts of 6-deoxy-3-O-Me-altro-heptose. Both CPSs were shown to carry O-methyl-phosphoramidate. The two genomes contained strain-specific zones, some of which could be traced to a plasmid origin, and both contained a large chromosomal insertion related to the CJEI3 element of C. jejuni RM1221. The genomes of both strains shared a high degree of similarity to each other and, with the exception of the capsule locus of CG8421, to the type strain of the HS3 serotype, TGH9011.
开展空肠弯曲菌疫苗的Ⅱ期攻毒研究将有助于疫苗的研发。然而,大多数空肠弯曲菌菌株的脂寡糖(LOS)与人神经节苷脂存在分子模拟现象,这给格林-巴利综合征的疫苗研发带来了安全隐患。通过DNA探针分析鉴定出了一些似乎缺乏合成神经节苷脂模拟物基因的空肠弯曲菌临床分离株。确定来自东南亚的两个临床分离株(菌株BH-01-0142和CG8421)表达含有N-乙酰奎诺糖胺的LOS类型。在这些菌株的LOS中未观察到神经节苷脂结构,对这两个菌株基因组的焦磷酸测序证实不存在参与神经节苷脂模拟的基因。确定BH-01-0142的荚膜多糖(CPS)由半乳糖(Gal)、6-脱氧-艾杜庚糖以及少量的D-甘油-D-艾杜庚糖组成,观察到CG8421的CPS含有Gal、6-脱氧-altro-庚糖、N-乙酰葡糖胺以及少量的6-脱氧-3-O-甲基-altro-庚糖。两种CPS均显示带有O-甲基磷酰胺酯。这两个基因组包含菌株特异性区域,其中一些区域可追溯到质粒来源,并且两个基因组都包含一个与空肠弯曲菌RM1221的CJEI3元件相关的大型染色体插入片段。这两个菌株的基因组彼此高度相似,并且除了CG8421的荚膜基因座外,与HS3血清型的模式菌株TGH9011高度相似。