Phase variation mediated niche adaptation during prolonged experimental murine infection with Helicobacter pylori
Phase variation mediated niche adaptation during prolonged experimental murine infection with Helicobacter pylori
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DOI：
10.1099/mic.0.27379-0
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发表时间：
2005-03-01
期刊：
影响因子：
2.8
通讯作者：
Saunders, NJ
中科院分区：
文献类型：
--
作者：
Salaün, L;Ayraud, S;Saunders, NJ
研究了幽门螺杆菌中最近重新定义的31个相变基因的重复序列的变化，在三个无关的幽门螺杆菌菌株中进行了长达一年的小鼠胃定植。在实验期的开始和结束之间，发现了10个基因(32%)的变化，这将改变所研究的三个菌株中的一个或多个的基因表达。对于那些在最长时间点出现重复长度变化的基因，中间时间点显示不同功能组基因的变化率不同。最有可能与即刻生态位匹配相关的基因变化最快，包括磷脂酶A(PldA)和脂多糖生物合成基因。其他可能处于适应性免疫选择下的表面蛋白变化较慢。限制性内切酶修饰基因没有表现出特定的时间模式。在对小鼠胃环境的适应过程中，阶段变化的基因的数量与它们的相对适合度成反比，正如先前在这种小鼠定植模型中所确定的那样。这表明这些基因在决定最初的适应殖民以及随后的生态位适应方面发挥了作用。此外，还研究了不控制实际基因表达的相变基因内的编码串联重复序列。在定殖过程中，发现该重复序列的拷贝数不同。这表明，串联重复序列编码的结构的变化也可能在幽门螺杆菌定植过程中蛋白功能改变和/或免疫逃避中发挥作用。
Changes in the repeats associated with the recently redefined repertoire of 31 phase-variable genes in Helicobacter pylori were investigated following murine gastric colonization for up to one year in three unrelated H. pylori strains. Between the beginning and end of the experimental period, changes were seen in ten genes (32%), which would alter gene expression in one or more of the three strains studied. For those genes that showed repeat length changes at the longest time points, intermediate time points showed differences between the rates of change for different functional groups of genes. Genes most likely to be associated with immediate niche fitting changed most rapidly, including phospholipase A (pldA) and LPS biosynthetic genes. Other surface proteins, which may be under adaptive immune selection, changed more slowly. Restriction-modification genes showed no particular temporal pattern. The number of genes that phase varied during adaptation to the murine gastric environment correlated inversely with their relative fitness as previously determined in this murine model of colonization. This suggests a role for these genes in determining initial fitness for colonization as well as in subsequent niche adaptation. In addition, a coding tandem repeat within a phase-variable gene which does not control actual gene expression was also investigated. This repeat was found to vary in copy number during colonization. This suggests that changes in the structures encoded by tandem repeats may also play a role in altered protein functions and/or immune evasion during H. pylori colonization.