Comparative genomic analysis of Campylobacter jejuni associated with Guillain-Barre and Miller Fisher syndromes:: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity
Comparative genomic analysis of Campylobacter jejuni associated with Guillain-Barre and Miller Fisher syndromes:: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity
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DOI：
10.1186/1471-2164-8-359
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发表时间：
2007-10-05
期刊：
影响因子：
4.4
通讯作者：
Nash, John H. E.
中科院分区：
文献类型：
--
作者：
Taboada, Eduardo N.;van Belkum, Alex;Nash, John H. E.
背景资料：空肠弯曲菌感染是最常见的前驱感染，可引发神经性疾病格林-巴利综合征（GBS）和米勒费舍尔综合征（MFS）。虽然唾液酸化神经节苷脂模拟脂寡糖（LOS）结构是C。空肠，它们似乎不是神经病性结果的唯一要求，因为能够产生它们的菌株已经从患有简单肠炎病例的患者中分离出来。因此，其他病原体和/或宿主相关因素导致神经系统并发症的发生。我们已经使用比较基因组杂交进行了详细的基因组比较菌株分离GBS/MFS和梅毒患者。我们的数据集，其中1712个基因的基因保守性分析了102株，包括56个神经致病性分离株，代表了最大的系统搜索C。空肠因素与GBS/MFS相关，使我们能够分析神经致病性C.结果：大多数GBS/MFS菌株可以被分配到六个主要谱系之一，这表明几个遗传背景可以导致神经致病性表型。基因保守率的统计分析表明，虽然基因参与的唾液酸化的LOS结构显着相关的神经致病性菌株，仍然有许多梅毒控制菌株都携带这些基因，并共享显着水平的基因组相似性与他们的神经致病性的同行。两个荚膜生物合成基因（Cj 1421 c和Cj 1428 c）在神经致病性菌株中显示出较高的保守率，与绦虫对照菌株相比。任何潜在的参与这些基因在神经发病机制必须进行评估。有一个基因（HS：3Cj 1135）在家蚕对照菌株中具有较高的保守率。该基因编码的葡萄糖基转移酶，被发现在一些LOS类，不表达神经节苷脂mimics.Conclusion：我们的研究结果证实，神经致病因素可能会转移之间的不相关的菌株不同的遗传背景。我们的研究结果还表明，从简单的肠炎病例中分离的一些菌株未能引起神经病理性临床结果可能是由于细微的遗传差异，沉默了它们的神经致病潜力和/或由于宿主相关的factors.The微阵列数据已保藏在NCBI的基因表达综合库中，保藏号为GSE 3579。
Background: Campylobacter jejuni infection represents the most frequent antecedent infection triggering the onset of the neuropathic disorders Guillain-Barre syndrome (GBS) and Miller Fisher syndrome (MFS). Although sialylated ganglioside-mimicking lipo-oligosaccharide (LOS) structures are the strongest neuropathogenic determinants in C. jejuni, they do not appear to be the only requirement for a neuropathic outcome since strains capable of their production have been isolated from patients with uncomplicated cases of enteritis. Consequently, other pathogen and/or host-related factors contribute to the onset of neurological complications. We have used comparative genomic hybridization to perform a detailed genomic comparison of strains isolated from GBS/MFS and enteritis-only patients. Our dataset, in which the gene conservation profile for 1712 genes was assayed in 102 strains, including 56 neuropathogenic isolates, represents the largest systematic search for C. jejuni factors associated with GBS/MFS to date and has allowed us to analyze the genetic background of neuropathogenic C. jejuni strains with an unprecedented level of resolution.Results: The majority of GBS/MFS strains can be assigned to one of six major lineages, suggesting that several genetic backgrounds can result in a neuropathogenic phenotype. A statistical analysis of gene conservation rates revealed that although genes involved in the sialylation of LOS structures were significantly associated with neuropathogenic strains, still many enteritis-control strains both bear these genes and share remarkable levels of genomic similarity with their neuropathogenic counterparts. Two capsule biosynthesis genes (Cj1421c and Cj1428c) showed higher conservation rates among neuropathogenic strains compared to enteritis-control strains. Any potential involvement of these genes in neuropathogenesis must be assessed. A single gene (HS: 3 Cj1135) had a higher conservation rate among enteritis-control strains. This gene encodes a glucosyltransferase that is found in some of the LOS classes that do not express ganglioside mimics.Conclusion: Our findings corroborate that neuropathogenic factors may be transferred between unrelated strains of different genetic background. Our results would also suggest that the failure of some strains isolated from uncomplicated cases of enteritis to elicit a neuropathic clinical outcome may be due to subtle genetic differences that silence their neuropathogenic potential and/or due to host-related factors.The microarray data has been deposited in NCBI's Gene Expression Omnibus under accession number GSE3579.