Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system.
Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system.
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DOI：
10.1099/mic.0.2007/016055-0
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Forsyth MH
中科院分区：
文献类型：
--
作者：
Goodwin AC;Weinberger DM;Ford CB;Nelson JC;Snider JD;Hall JD;Paules CI;Peek RM;Forsyth MH
适应酸性微环境和粘附于粘膜上皮是幽门螺杆菌在人胃中持续定植的必要条件。SabA（一种与H.幽门螺杆菌粘附到宿主胃上皮细胞，可以通过位于启动子区和编码区的重复核苷酸束中的滑动链错配的相位变化来调节。本研究表明，在sabA基因座发生相位变化的个别菌株的H。pylori，以及来自单个患者的多个分离株。此外，sabA的转录在体外被酸响应的ArsRS双组分信号转导系统抑制。我们的结果表明，arsS（jhp 0151/HP 0165）组氨酸激酶基因座的同基因失活导致菌株J 99（包含符合读码框的sabA等位基因）中胃上皮细胞的粘附性增加10倍，但在菌株26695（超出读码框的sabA等位基因）中则不然。ArsRS双组分信号转导系统对sabA基因座的转录调控和染色体复制过程中通过滑动链错配产生携带交替sabA等位基因的亚群的组合可以允许H.幽门螺杆菌快速适应不同的微环境或宿主免疫反应。作为一种缺乏调节蛋白的病原体，这种双重调节表明SabA的表达在H.幽门感染
Adaptation to the acidic microenvironment, and adherence to mucosal epithelium, are essential for persistent colonization of the human stomach by Helicobacter pylori. The expression of SabA, an adhesin implicated in the ability of H. pylori to adhere to the host gastric epithelium, can be modulated by phase variation via slipped-strand mispairing in repetitive nucleotide tracts located in both the promoter region and the coding region. This study demonstrates the occurrence of phase variation at the sabA locus within individual strains of H. pylori, and among multiple isolates from a single patient. In addition, transcription of sabA is repressed by the acid-responsive ArsRS two-component signal transduction system in vitro. Our results demonstrate that isogenic inactivation of the arsS (jhp0151/HP0165) histidine kinase locus results in a 10-fold SabA-dependent increase in adherence to gastric epithelial cells in strain J99 (contains an in-frame sabA allele), but not in strain 26695 (out-of-frame sabA allele). The combination of transcriptional regulation of the sabA locus by the ArsRS two-component signal-transduction system and the generation of subpopulations harbouring alternate sabA alleles by slipped-strand mispairing during chromosomal replication could permit H. pylori to rapidly adapt to varying microenvironments or host immune responses. As a pathogen with a paucity of regulatory proteins, this dual regulation indicates that SabA expression is a tightly regulated process in H. pylori infection.
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影响因子：
3.1
作者：
Loh, JT;Cover, TL
通讯作者：
Cover, TL
影响因子：
3.2
作者：
Beier, D;Frank, R
通讯作者：
Frank, R
DOI：
10.1073/pnas.0702412104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Mrazek, Jan;Guo, Xiangxue;Shah, Apurva
通讯作者：
Shah, Apurva
影响因子：
2.1
作者：
Pflock, M;Dietz, P;Beier, D
通讯作者：
Beier, D
影响因子：
3.1
作者：
Lehours, P;Ménard, A;Mégraud, F
通讯作者：
Mégraud, F