Phase-variable restriction/modification systems are required for Helicobacter pylori colonization
Phase-variable restriction/modification systems are required for Helicobacter pylori colonization
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DOI：
10.1186/s13099-014-0035-z
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发表时间：
2014-09-05
期刊：
影响因子：
4.2
通讯作者：
Benghezal, Mohammed
中科院分区：
文献类型：
--
作者：
Gauntlett, Jonathan C.;Nilsson, Hans-Olof;Benghezal, Mohammed
背景：细菌病原体用于宿主适应和免疫逃避的一种机制是通过相变产生表型多样性，这是由限制性修饰（RM）系统内相变甲基转移酶活性调节的一组基因的差异表达引起的。相变在幽门螺杆菌中很活跃，但目前还没有研究探讨相变RM系统对宿主定植的意义。方法：构建了两种不能相变的突变体类型；干净删除突变体（“DEL”）和突变体（“ON”），其中同聚重复序列被非重复同义序列取代，从而表达全长蛋白质。评估所得突变体在小鼠模型中的定植能力。结果：在幽门螺杆菌 OND79 中发现了编码甲基转移酶或 RM 系统成员的五个相变基因。我们的突变体分为三类： 1，对定植几乎没有影响的；2，全长蛋白表达有害的；3，两种突变都有害的。结论：我们的结果表明，相变甲基转移酶对幽门螺杆菌定植至关重要，表明基因组甲基化和表观遗传多样性的产生对于定植和发病机制很重要。第三类突变体表明，通过相变实现的幽门螺杆菌细胞群的差异基因组甲基化状态对于宿主适应至关重要。对属于另外两个类别的相变 RM 突变体的研究（不严格要求定植）代表了研究相变在幽门螺杆菌持久性中的作用的未来前景。
Background: One mechanism utilized by bacterial pathogens for host adaptation and immune evasion is the generation of phenotypic diversity by the phasevarion that results from the differential expression of a suite of genes regulated by the activity of a phase-variable methyltransferase within a restriction modification (RM) system. Phasevarions are active in Helicobacter pylori, however there have been no studies investigating the significance of phase-variable RM systems on host colonization.Methods: Two mutant types incapable of phase variation were constructed; a clean deletion mutant ('DEL') and a mutant ('ON') where the homopolymeric repeat was replaced with a non-repeat synonymous sequence, resulting in expression of the full-length protein. The resulting mutants were assessed for their colonisation ability in the mouse model.Results: Five phase-variable genes encoding either methyltransferases or members of RM systems were found in H. pylori OND79. Our mutants fell into three categories; 1, those with little effect on colonization, 2, those where expression of the full-length protein was detrimental, 3, those where both mutations were detrimental.Conclusions: Our results demonstrated that phase-variable methyltransferases are critical to H. pylori colonization, suggesting that genome methylation and generation of epigenetic diversity is important for colonization and pathogenesis. The third category of mutants suggests that differential genome methylation status of H. pylori cell populations, achieved by the phasevarion, is essential for host adaptation. Studies of phase-variable RM mutants falling in the two other categories, not strictly required for colonization, represent a future perspective to investigate the role of phasevarion in persistence of H. pylori.