ChePep controls Helicobacter pylori Infection of the gastric glands and chemotaxis in the Epsilonproteobacteria.
ChePep controls Helicobacter pylori Infection of the gastric glands and chemotaxis in the Epsilonproteobacteria.
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作者：
Howitt MR;Lee JY;Lertsethtakarn P;Vogelmann R;Joubert LM;Ottemann KM;Amieva MR
微生物利用定向运动来定殖恶劣和动态的环境。我们发现幽门螺杆菌菌株在胃腺深处建立细菌菌落，并鉴定出一种新的蛋白质ChePep，它是定植在这个小生境中所必需的。ChePep优先定位于鞭毛杆。虽然缺乏ChePep的突变体具有正常的鞭毛超微结构和能动性，但它们在群集能力方面有轻微缺陷。通过跟踪单个细菌的运动，我们发现，Cheppep突变体不能控制其鞭毛的旋转，并且以异常频繁的反转进行游泳。这些突变体甚至可以用鞭毛拉着细菌向后运动。趋化性信号通路的遗传分析表明，ChePep通过趋化系统调节鞭毛旋转。通过在微观pH梯度内检查幽门螺杆菌，我们确定ChePep对调节趋化行为至关重要。chePep基因是唯一的ε变形菌，但发现整个这个多样化的群体。我们在幽门螺杆菌中表达了来自Epsilonproteobacteria其他成员的ChePep，包括人畜共患病病原体空肠弯曲杆菌和深海热液喷口居民Caminibacter mediatlanticus，并发现ChePep在该类中功能保守。ChePep代表了Epsilonproteobacteria特有的一个新的趋化调节因子家族，并说明了微生物进化来控制运动的不同策略。 幽门螺杆菌菌株感染全世界一半的人类，并有助于消化性溃疡和胃癌的发展。幽门螺杆菌不能在胃的酸性腔中存活，并使用鞭毛主动游向并定殖保护性粘液和上皮。趋化系统通过调节鞭毛的旋转来使幽门螺杆菌导航。我们发现了一种新的蛋白质，ChePep，它控制幽门螺杆菌的趋化性。ChePep突变体不能在小鼠的胃腺中定植，并且完全被正常的幽门螺杆菌所击败。编码ChePep的基因仅在Epsilonproteobacteria类中发现，其中包括人类病原体空肠弯曲杆菌和环境微生物，如深海热液喷口殖民者Caminibacter mediatlanticus，我们表明ChePep功能在该类中是保守的。我们的研究确定了幽门螺杆菌中的一个新的定植因子，也为细菌趋化性的控制和进化提供了见解。
Microbes use directed motility to colonize harsh and dynamic environments. We discovered that Helicobacter pylori strains establish bacterial colonies deep in the gastric glands and identified a novel protein, ChePep, necessary to colonize this niche. ChePep is preferentially localized to the flagellar pole. Although mutants lacking ChePep have normal flagellar ultrastructure and are motile, they have a slight defect in swarming ability. By tracking the movement of single bacteria, we found that ∆ChePep mutants cannot control the rotation of their flagella and swim with abnormally frequent reversals. These mutants even sustain bursts of movement backwards with the flagella pulling the bacteria. Genetic analysis of the chemotaxis signaling pathway shows that ChePep regulates flagellar rotation through the chemotaxis system. By examining H. pylori within a microscopic pH gradient, we determined that ChePep is critical for regulating chemotactic behavior. The chePep gene is unique to the Epsilonproteobacteria but is found throughout this diverse group. We expressed ChePep from other members of the Epsilonproteobacteria, including the zoonotic pathogen Campylobacter jejuni and the deep sea hydrothermal vent inhabitant Caminibacter mediatlanticus, in H. pylori and found that ChePep is functionally conserved across this class. ChePep represents a new family of chemotaxis regulators unique to the Epsilonproteobacteria and illustrates the different strategies that microbes have evolved to control motility. Helicobacter pylori strains infect half of all humans worldwide and contribute to the development of peptic ulcers and gastric cancer. H. pylori cannot survive within the acidic lumen of the stomach and uses flagella to actively swim to and colonize the protective mucus and epithelium. The chemotaxis system allows H. pylori to navigate by regulating the rotation of its flagella. We identified a new protein, ChePep, which controls chemotaxis in H. pylori. ChePep mutants fail to colonize the gastric glands of mice and are completely outcompeted by normal H. pylori. Genes encoding ChePep are found only in the class Epsilonproteobacteria, which includes the human pathogen Campylobacter jejuni and environmental microbes like the deep-sea hydrothermal vent colonizer Caminibacter mediatlanticus, and we show that ChePep function is conserved in this class. Our study identifies a new colonization factor in H. pylori and also provides insight into the control and evolution of bacterial chemotaxis.