Helicobacter pylori genome evolution during human infection

Helicobacter pylori genome evolution during human infection
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DOI:
10.1073/pnas.1018444108
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发表时间:
2011-03-22
影响因子:
11.1
通讯作者:
Suerbaum, Sebastian
Suerbaum, Sebastian
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kennemann, Lynn;Didelot, Xavier;Suerbaum, Sebastian

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高度遗传多样性是胃病原体幽门螺杆菌的标志。我们使用454测序技术对五组H. pylori菌株是从四名慢性感染的哥伦比亚人(分离间隔= 3-16年)和一名实验性感染H. pylori作为疫苗试验的一部分。哥伦比亚H. pylori的差异在于27-232个分离的SNP和16-441个由重组产生的输入多态性簇。输入序列(平均长度= 394 bp)在染色体上呈非随机分布,且经常发生在群体中,表明H.幽门螺杆菌首先吸收长的DNA片段,随后部分整合成多个较短的片段。进口目前在显着增加的频率在啤酒花家族的外膜基因旁系同源物,其中一些涉及细菌粘附,这表明多样化的选择。在一个感染志愿者的菌株对中没有发现重组的证据,也没有发现其他的差异,这表明H。pylori基因组在没有混合感染的情况下是稳定的。在这些少数的差异是一个OFF/ON开关的相位可变的粘附素基因hopZ,这表明强有力的体内选择,这种假定的粘附素在早期殖民。
High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals = 3-16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27-232 isolated SNPs and 16-441 imported clusters of polymorphisms resulting from recombination. Imports (mean length = 394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization.