Structural and Functional Diversity of Lipid A from Helicobacter pylori

本研究通过对幽门螺杆菌脂质A结构和功能的多样性及其变化的研究，探讨脂质A的结构、免疫生物学活性、感染性（胃内定殖能力）与各种疾病的关系。通过建立负离子模式ESI-MS和MALDI-TOF/MS结合改良的TLC印迹法快速筛选方法，评价在不同培养条件下从不同菌株或批次获得的幽门螺杆菌。检测到四种不同的结构。最主要的形式是HPLA_1549，其次是HPLA_1295。结果表明，经反复培养后，这些结构均变为HPLA_1506和HPLA_1252，而细菌的形态没有发生变化。评价了这些脂质As对人外周血全血细胞或人外周血单核细胞的细胞因子诱导活性。除了HPLA_1295的IL-6诱导活性较弱但明显外，它们几乎没有产生炎性细胞因子如肿瘤坏死因子α、白细胞介素（IL）-12或干扰素-γ的活性。相反，脂质As显示出高的IL-18诱导活性。发现具有IL-6诱导型脂质A结构的菌株（HPLA_1295）对C57 BL/6小鼠的感染具有统计学上的高得分，表明脂质A结构与感染之间的关系。

This study was focused on the structural and functional diversity and change for lipid A from Helicobactor pylori to evaluate the relationship between the structure of lipid A, its immunobiological activities, the infective activity (potency of colonization in stomach) of strains, and varied diseases. By our established quick screening procedure in terms of negative mode ESI-and MALDI-TOF/MS combined with the modified TLC blotting, lipid As of over 40 H. pylori bacteria obtained from different strains or from batches under different culture conditions were evaluated. Four distinct structures were detected. The most predominant form was HPLA_1549 and the second was HPLA_1295. It was found that those structures were changed to HPLA_1506 and HPLA_1252 by the repeated cultivation, but not by the morphological change of the bacteria. The cytokine inducing activities from human peripheral whole blood cells or from human peripheral blood mononuclear cells were evaluated on these lipid As. They possessed very weak, almost no, activities for the production of inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12 or interferon-γ, except for the weak but distinct IL-6 inducing activity of one structure, HPLA_1295. In contrast, the lipid As showed high IL-18 inducing activity. It was found that strains possessing the IL-6 inducible lipid A structure (HPLA_1295) had statistically high score for the infection against C57BL/6 mice, suggesting a relation between lipid A structure and infection.