Merkx-Jacques A, Obhi R K, Bethune G, Creuzenet C
Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
J Bacteriol. 2004 Apr;186(8):2253-65. doi: 10.1128/JB.186.8.2253-2265.2004.
flaA1 and wbpB are conserved genes with unknown biological function in Helicobacter pylori. Since both genes are predicted to be involved in lipopolysaccharide (LPS) biosynthesis, flagellum assembly, or protein glycosylation, they could play an important role in the pathogenesis of H. pylori. To determine their biological role, both genes were disrupted in strain NCTC 11637. Both mutants exhibited altered LPS, with loss of most O-antigen and core modification, and increased sensitivity to sodium dodecyl sulfate compared to wild-type bacteria. These defects could be complemented in a gene-specific manner. Also, flaA1 could complement these defects in the wbpB mutant, suggesting a potential redundancy of the reductase activity encoded by both genes. Both mutants were nonmotile, although the wbpB mutant still produced flagella. The defect in the flagellum functionality of this mutant was not due to a defect in flagellin glycosylation since flagellins from wild-type strain NCTC 11637 were shown not to be glycosylated. The flaA1 mutant produced flagellins but no flagellum. Overall, the similar phenotypes observed for both mutants and the complementation of the wbpB mutant by flaA1 suggest that both genes belong to the same biosynthesis pathway. The data also suggest that flaA1 and wbpB are at the interface between several pathways that govern the expression of different virulence factors. We propose that FlaA1 and WbpB synthesize sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production and that glycosylation regulates the activity of these proteins.
flaA1和wbpB是幽门螺杆菌中具有未知生物学功能的保守基因。由于预测这两个基因都参与脂多糖（LPS）生物合成、鞭毛组装或蛋白质糖基化，它们可能在幽门螺杆菌的发病机制中发挥重要作用。为了确定它们的生物学作用，在NCTC 11637菌株中破坏了这两个基因。与野生型细菌相比，两个突变体均表现出LPS改变，大部分O抗原和核心修饰缺失，并且对十二烷基硫酸钠的敏感性增加。这些缺陷可以以基因特异性方式得到互补。此外，flaA1可以互补wbpB突变体中的这些缺陷，表明这两个基因编码的还原酶活性可能存在冗余。两个突变体均无运动能力，尽管wbpB突变体仍产生鞭毛。该突变体鞭毛功能的缺陷不是由于鞭毛蛋白糖基化缺陷，因为野生型NCTC 11637菌株的鞭毛蛋白未显示被糖基化。flaA1突变体产生鞭毛蛋白但不产生鞭毛。总体而言，两个突变体观察到的相似表型以及flaA1对wbpB突变体的互补表明这两个基因属于同一生物合成途径。数据还表明，flaA1和wbpB处于控制不同毒力因子表达的几种途径的界面。我们提出，FlaA1和WbpB合成专门用于参与LPS和鞭毛产生的蛋白质糖基化的糖衍生物，并且糖基化调节这些蛋白质的活性。
