Salaün Laurence, Linz Bodo, Suerbaum Sebastian, Saunders Nigel J
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Max-Planck-Institut fuer Infektionsbiologie, Dept. Molecular Biology, Schumannstrasse 21/22, D-10117 Berlin, Germany.
Microbiology (Reading). 2004 Apr;150(Pt 4):817-830. doi: 10.1099/mic.0.26993-0.
Phase variation is a common mechanism used by pathogenic bacteria to generate intra-strain diversity that is important in niche adaptation and is strongly associated with virulence determinants. Previous analyses of the complete sequences of the Helicobacter pylori strains 26695 and J99 have identified 36 putative phase-variable genes among the two genomes through their association with homopolymeric tracts and dinucleotide repeats. Here a comparative analysis of the two genomes is reported and an updated and expanded list of 46 candidate phase-variable genes in H. pylori is described. These have been systematically investigated by PCR and sequencing for the presence of the genes, and the presence and variability in length of the repeats in strains 26695 and J99 and in a collection of unrelated H. pylori strains representative of the main global subdivisions recently suggested. This provides supportive evidence for the phase variability of 30 of the 46 candidates. Other differences in this subset of genes were observed (i) in the repeats, which can be present or absent among the strains, or stabilized in different strains and (ii) in the gene-complements of the strains. Differences between genes were not consistently correlated with the geographic population distribution of the strains. This study extends and provides new evidence for variation of this type in H. pylori, and of the high degree of diversity of the repertoire of genes which display phase-variable switching within individual strains.
相变是病原菌用于产生菌株内多样性的一种常见机制,这种多样性在生态位适应中很重要,并且与毒力决定因素密切相关。先前对幽门螺杆菌菌株26695和J99完整序列的分析,通过与同聚物序列和二核苷酸重复序列的关联,在这两个基因组中鉴定出36个假定的相变基因。本文报道了对这两个基因组的比较分析,并描述了幽门螺杆菌中46个候选相变基因的更新和扩展列表。通过PCR和测序系统地研究了这些基因的存在情况,以及菌株26695和J99以及最近提出的代表主要全球亚群的一组无关幽门螺杆菌菌株中重复序列的存在情况和长度变异性。这为46个候选基因中的30个基因的相变变异性提供了支持性证据。在这个基因子集中还观察到其他差异:(i)在重复序列方面,菌株之间可能存在或不存在,或者在不同菌株中稳定存在;(ii)在菌株的基因互补方面。基因之间的差异与菌株的地理种群分布并不一致相关。本研究扩展并为幽门螺杆菌中这种类型的变异以及在单个菌株内显示相变开关的基因库的高度多样性提供了新的证据。