Multi-omics approaches to deciphering a hypervirulent strain of Campylobacter jejuni.

Multi-omics approaches to deciphering a hypervirulent strain of Campylobacter jejuni.
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DOI:
10.1093/gbe/evt172
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发表时间:
2013
影响因子:
3.3
通讯作者:
Zhang Q
Zhang Q
中科院分区:
生物学2区
文献类型:
--
作者:
Wu Z;Sahin O;Shen Z;Liu P;Miller WG;Zhang Q

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空肠弯曲杆菌克隆SA最近成为美国绵羊流产的主要原因,也与人类食源性胃肠炎有关。该克隆的一个独特表型是其诱导菌血症和流产的能力。为了便于理解这种高毒力克隆的发病机制,我们使用多组学方法分析了克隆SA的临床分离株(IA 3902)。IA 3902的基因组含有一条1,635,045 bp的环状染色体和一个37,174 bp的环状质粒。比较基因组分析表明,IA 3902与C. jejuni NCTC 11168,其是参考菌株,并且先前显示在妊娠动物中是非流产性的。尽管基因组具有高度的同线性和序列同源性,但两个基因组之间存在12个可变区(VR)和8,696个单核苷酸多态性和indel。值得注意的是,IA 3902的荚膜多糖生物合成和O-连接糖基化位点中的可变基因与C.空肠亚种doylei和C.空肠G1,这是已知的经常与菌血症。通过转录组学和蛋白质组学分析比较了IA 3902和NCTC 11168,结果表明IA 3902的能量生成、运动性和丝氨酸利用途径显著上调,而铁吸收和脯氨酸、谷氨酸、天冬氨酸和乳酸利用途径显著下调。这些结果表明C.空肠克隆SA已经进化出不同的基因组内容和基因表达模式,其调节表面多糖结构、运动性和代谢途径。这些变化可能导致其在流产诱导中的超强毒力。
Campylobacter jejuni clone SA recently emerged as the predominant cause of sheep abortion in the United States and is also associated with foodborne gastroenteritis in humans. A distinct phenotype of this clone is its ability to induce bacteremia and abortion. To facilitate understanding the pathogenesis of this hypervirulent clone, we analyzed a clinical isolate (IA3902) of clone SA using multi-omics approaches. The genome of IA3902 contains a circular chromosome of 1,635,045 bp and a circular plasmid of 37,174 bp. Comparative genomic analysis revealed that IA3902 is most closely related to C. jejuni NCTC11168, which is a reference strain and was previously shown to be non-abortifacient in pregnant animals. Despite the high genomic synteny and sequence homology, there are 12 variable regions (VRs) and 8,696 single-nucleotide polymorphisms and indels between the two genomes. Notably, the variable genes in the capsular polysaccharides biosynthesis and O-linked glycosylation loci of IA3902 are highly homogenous to their counterparts in C. jejuni subsp. doylei and C. jejuni G1, which are known to be frequently associated with bacteremia. Transcriptomic and proteomic profiles were conducted to compare IA3902 with NCTC11168, which revealed that the pathways of energy generation, motility, and serine utilization were significantly up-regulated in IA3902, whereas the pathways of iron uptake and proline, glutamate, aspartate, and lactate utilization were significantly down-regulated. These results suggest that C. jejuni clone SA has evolved distinct genomic content and gene expression patterns that modulate surface polysacharide structures, motilitiy, and metabolic pathways. These changes may have contributed to its hyper-virulence in abortion induction.
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