Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil
Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil
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DOI：
10.1128/iai.00750-13
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Josenhans, Christine
中科院分区：
文献类型：
--
作者：
Behrens, Wiebke;Schweinitzer, Tobias;Josenhans, Christine
幽门螺杆菌通过一组有限的传感器来维持其在人类宿主中的定植。TlpD是一种被提出的幽门螺杆菌能量趋向性传感器，在细菌产能较低的环境条件下占优势。我们利用沙鼠感染模型研究了幽门螺杆菌TlpD对体内定植的影响，该模型与人类的胃生理非常相似。一种适应沙鼠的幽门螺杆菌菌株HP87 P7表现出能量依赖行为，而其等基因tlpD突变体则失去了能量依赖行为。补充了tlpd的菌株恢复了野生型表型。补充菌株对沙鼠的感染表明，TlpD对腔体和体腔的持续感染很重要，并提示TlpD在水平导航和持续的体腔定植中起作用。为了充分表征该模型并深入了解幽门螺旋杆菌对沙鼠适应的遗传基础，我们测定了沙鼠适应菌株HP87 P7、两个HP87 P7 tlpD突变体在沙鼠传代前后以及原始人类分离株HP87的全基因组序列。沙鼠适应后，基因组的完整性，包括功能性cag致病性岛的完整性得以维持。观察了菌株间的遗传和表型差异。沙鼠适应菌株和人类分离菌株之间的主要差异出现了，包括最近重组的证据。在聚焦转移酶基因futC （HP0093）中选择tlpD突变体通过沙鼠获得功能变异。总之，具有稳定基因组的沙鼠适应幽门螺杆菌菌株有助于确定TlpD在胃中持久定植的重要功能。
Helicobacter pylori maintains colonization in its human host using a limited set of taxis sensors. TlpD is a proposed energy taxis sensor of H. pylori and dominant under environmental conditions of low bacterial energy yield. We studied the impact of H. pylori TlpD on colonization in vivo using a gerbil infection model which closely mimics the gastric physiology of humans. A gerbil-adapted H. pylori strain, HP87 P7, showed energy-dependent behavior, while its isogenic tlpD mutant lost it. A TlpD-complemented strain regained the wild-type phenotype. Infection of gerbils with the complemented strain demonstrated that TlpD is important for persistent infection in the antrum and corpus and suggested a role of TlpD in horizontal navigation and persistent corpus colonization. As a part of the full characterization of the model and to gain insight into the genetic basis of H. pylori adaptation to the gerbil, we determined the complete genome sequences of the gerbil-adapted strain HP87 P7, two HP87 P7 tlpD mutants before and after gerbil passage, and the original human isolate, HP87. The integrity of the genome, including that of a functional cag pathogenicity island, was maintained after gerbil adaptation. Genetic and phenotypic differences between the strains were observed. Major differences between the gerbil-adapted strain and the human isolate emerged, including evidence of recent recombination. Passage of the tlpD mutant through the gerbil selected for gain-of-function variation in a fucosyltransferase gene, futC (HP0093). In conclusion, a gerbil-adapted H. pylori strain with a stable genome has helped to establish that TlpD has important functions for persistent colonization in the stomach.