The Helicobacter pylori chemotaxis receptor TlpB (HP0103) is required for pH taxis and for colonization of the gastric mucosa
The Helicobacter pylori chemotaxis receptor TlpB (HP0103) is required for pH taxis and for colonization of the gastric mucosa
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DOI：
10.1128/jb.188.7.2656-2665.2006
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发表时间：
2006-04-01
影响因子：
3.2
通讯作者：
Hoffman, PS
中科院分区：
文献类型：
--
作者：
Croxen, MA;Sisson, G;Hoffman, PS
幽门螺杆菌在哺乳动物胃粘膜中的位置由胃粘液内的自然pH梯度限定，胃粘液在粘膜上皮细胞附近更呈碱性，而在管腔附近更呈酸性。我们已经使用了显微镜载玻片为基础的pH梯度测定和视频数据收集系统来记录pH-战术行为。H.幽门螺杆菌改变其游动模式，从直线随机游动到弧形或圆形模式，使能动群体远离强酸。碱性区域的细菌不会游向酸性，这表明pH趋化性是一种负趋化性。为了鉴定负责pH-趋化信号转导的化学感受器，使用无载体等位基因置换策略在H. pylori菌株SS 1和菌株KE 26695的运动变体。所有的缺失突变体都是能动的，并显示在布鲁氏菌软琼脂正常的趋化性，但只有tlpB突变体的pH值的趋化性缺陷。tlpD突变体表现出更多的翻滚和弧形游泳，而tlpC突变体是hypermotile和响应酸。尽管tlpA、tlpC和tlpD突变体在小鼠中定殖至接近野生型水平，但tlpB突变体在高度容许的C57 BL/6白细胞介素-12（IL-12）（p40（-/-））缺陷小鼠中的定殖是缺陷的。互补的tlpB突变体（从rdxA基因座表达的tlpB）恢复小鼠的pH趋性和感染性。pH趋化性，如运动性和尿素酶活性，是必不可少的殖民和持久性在胃粘膜中，因此TlpB功能可能代表一个新的目标，在发展的治疗方法，盲目的战术行为。
The location of Helicobacter pylori in the gastric mucosa of mammals is defined by natural pH gradients within the gastric mucus, which are more alkaline proximal to the mucosal epithelial cells and more acidic toward the lumen. We have used a microscope slide-based pH gradient assay and video data collection system to document pH-tactic behavior. In response to hydrochloric acid (HCI), H. pylori changes its swimming pattern from straight-line random swimming to arcing or circular patterns that move the motile population away from the strong acid. Bacteria in more-alkaline regions did not swim toward the acid, suggesting the pH taxis is a form of negative chemotaxis. To identify the chemoreceptor(s) responsible for the transduction of pH-tactic signals, a vector-free allelic replacement strategy was used to construct mutations in each of the four annotated chemoreceptor genes (tlpA, tlpB, tlpC, and tlpD) in H. pylori strain SS1 and a motile variant of strain KE26695. All deletion mutants were motile and displayed normal chemotaxis in brucella soft agar, but only tlpB mutants were defective for pH taxis. tlpD mutants exhibited more tumbling and arcing swimming, while tlpC mutants were hypermotile and responsive to acid. While tlpA, tlpC, and tlpD mutants colonized mice to near wild-type levels, tlpB mutants were defective for colonization of highly permissive C57BL/6 interleukin-12 (IL-12) (p40(-/-)) -deficient mice. Complementation of the tlpB mutant (tlpB expressed from the rdxA locus) restored pH taxis and infectivity for mice. pH taxis, like motility and urease activity, is essential for colonization and persistence in the gastric mucosa, and thus TlpB function might represent a novel target in the development of therapeutics that blind tactic behavior.