Iron and pH homeostasis intersect at the level of fur regulation in the gastric pathogen Helicobacter pylori
Iron and pH homeostasis intersect at the level of fur regulation in the gastric pathogen Helicobacter pylori
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DOI：
10.1128/iai.74.1.602-614.2006
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Merrell, DS
中科院分区：
文献类型：
--
作者：
Gancz, H;Censini, S;Merrell, DS
幽门螺杆菌持续定植于世界上大多数人口的胃中，并且由于其在多种胃病中的因果作用而成为巨大的医疗负担。由于胃是一个不断变化的环境，H.这个生态位内的幽门需要调节细菌基因表达以科普环境波动。In H.幽门螺杆菌的铁吸收调节因子（Fur）在细菌适应胃粘膜内已知的两种条件（铁限制和低pH）中起着复杂的作用。pylori，我们表明，毛皮是所需的蒙古沙鼠的有效定植：突变株表现出100倍的增加，在50%的感染剂量，以及100倍的缺陷，在竞争性定植，当与野生型细菌共感染。此外，我们使用DNA微阵列，以确定其表达在毛皮缺陷株改变的基因。我们发现H.幽门螺杆菌由大约30个基因组成，其中大多数基因先前已被注释为与酸应激相关。最后，我们调查的作用，毛皮酸响应调制的基因表达，并表明，大量的基因异常表达的毛皮突变体，特别是在酸暴露。这一事实可能解释了这种调节剂在胃中生长和定植的需要。
Helicobacter pylori persistently colonizes the stomach of the majority of the world's population and is a tremendous medical burden due to its causal role in diverse gastric maladies. Since the stomach is a constantly changing environment, successful colonization of H. pylori within this niche requires regulation of bacterial gene expression to cope with the environmental fluctuations. In H. pylori, the ferric uptake regulator (Fur) has been shown to play an intricate role in adaptation of the bacterium to two conditions known to oscillate within the gastric mucosa: iron limitation and low pH. To extend our knowledge of the process of regulation and adaptation in H. pylori, we show that Fur is required for efficient colonization of the Mongolian gerbil: the mutant strain exhibits a 100-fold increase in the 50% infectious dose, as well as a 100-fold defect in competitive colonization, when coinfected with wild-type bacteria. Furthermore, we used DNA microarrays to identify genes whose expression was altered in a Fur-deficient strain. We show that the Fur regulon of H. pylori consists of approximately 30 genes, most of which have been previously annotated as acid stress associated. Finally, we investigate the role of Fur in acid-responsive modulation of gene expression and show that a large number of genes are aberrantly expressed in the Fur mutant specifically upon acid exposure. This fact likely explains the requirement for this regulator for growth and colonization in the stomach.