It is now well established that the Gram-negative bacterium, Helicobacter pylori, causes gastritis in humans. In recent years, it has become apparent that the so-called non-pylori Helicobacters, normally infecting pigs, cats, and dogs, may also be involved in human pathology via zoonotic transmission. Indeed, more than 30 species of non-pylori Helicobacters have been identified thus far. One such organism is Helicobacter canadensis, an emerging pathogen whose genome sequence was published in 2009. Given our long-standing interest in the biosynthesis of N-formylated sugars found in the O-antigens of some Gram-negative bacteria, we were curious as to whether H. canadensis produces such unusual carbohydrates. Here, we demonstrate using both biochemical and structural techniques that the proteins encoded by the HCAN_0198, HCAN_0204, and HCAN_0200 genes in H. canadensis, correspond to a 3,4-ketoisomerase, a pyridoxal 5′-phosphate aminotransferase, and an N-formyltransferase, respectively. For this investigation, five high-resolution X-ray structures were determined and the kinetic parameters for the isomerase and the N-formyltransferase were measured. Based on these data, we suggest that the unusual sugar, 3-formamido-3,6-dideoxy-d-glucose, will most likely be found in the O-antigen of H. canadensis. Whether N-formylated sugars found in the O-antigen contribute to virulence is presently unclear, but it is intriguing that they have been observed in such pathogens as Francisella tularensis, Mycobacterium tuberculosis, and Brucella melitensis.

中文翻译：

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研究新出现的人类病原体加拿大螺杆菌中一种不寻常的甲酰化糖的生物合成所需的酶

现在已经确定革兰氏阴性细菌幽门螺杆菌会导致人类胃炎。近年来，很明显，通常感染猪、猫和狗的所谓非幽门螺杆菌也可能通过人畜共患传播参与人类病理。事实上，迄今已鉴定出30 多种非幽门螺杆菌。一种这样的生物是加拿大螺杆菌，它是一种新兴病原体，其基因组序列于 2009 年发表。鉴于我们长期以来对在一些革兰氏阴性细菌的 O 抗原中发现的N甲酰化糖的生物合成感兴趣，我们很好奇H. canadensis是否产生如此不寻常的碳水化合物。在这里，我们使用生化和结构技术证明了由HCAN_0198、HCAN_0204和HCAN_0200基因编码的蛋白质在H. canadensis 中对应于 3,4-酮异构酶、吡哆醛 5'-磷酸氨基转移酶和N-甲酰基转移酶， 分别。对于这项研究，确定了五种高分辨率 X 射线结构，并测量了异构酶和N-甲酰基转移酶的动力学参数。基于这些数据，我们认为不寻常的糖 3-formamido-3,6-dideoxy- d - glucose 很可能存在于H. canadensis的 O 抗原中. 在 O 抗原中发现的N甲酰化糖是否有助于毒力目前尚不清楚，但有趣的是，它们已在土拉弗朗西斯菌、结核分枝杆菌和地中海布鲁氏菌等病原体中观察到。