BabA-mediated adherence of pediatric ulcerogenic H. pylori strains to gastric mucins at neutral and acidic pH

Helicobacter pylori infection can result in non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), adenocarcinoma, and gastric lymphoma. H. pylori reside within the gastric mucus layer, mainly composed of mucins carrying an array of glycan structures that can serve as bacterial adhesion epitopes. The aim of the present study was to characterize the binding ability, adhesion modes, and growth of H. pylori strains from pediatric patients with NUD and PUD to gastric mucins. Our results showed an increased adhesion capacity of pediatric PUD H. pylori strains to human and rhesus monkey gastric mucins compared to the NUD strains both at neutral and acidic pH, regardless if the mucins were positive for Lewis b (Leb), Sialyl-Lewis x (SLex) or LacdiNAc. In addition to babA positive strains being more common among PUD associated strains, H. pylori babA positive strains bound more avidly to gastric mucins than NUD babA positive strains at acidic pH. Binding to Leb was higher among babA positive PUD H. pylori strains compared to NUD strains at neutral, but not acidic, pH. PUD derived babA-knockout mutants had attenuated binding to mucins and Leb at acidic and neutral pH, and to SLex and DNA at acidic pH. The results highlight the role of BabA-mediated adherence of pediatric ulcerogenic H. pylori strains, and points to a role for BabA in adhesion to charged structures at acidic pH, separate from its specific blood group binding activity.幽门螺杆菌（Helicobacter pylori）感染可引发非溃疡性消化不良（non-ulcer dyspepsia，NUD）、消化性溃疡病（peptic ulcer disease，PUD）、腺癌以及胃淋巴瘤。幽门螺杆菌定植于胃黏液层中，该层主要由携带一系列可作为细菌黏附表位的聚糖结构的黏蛋白构成。本研究旨在表征来自非溃疡性消化不良与消化性溃疡病儿科患者的幽门螺杆菌菌株对胃黏蛋白的结合能力、黏附模式与生长特性。 我们的研究结果显示，无论黏蛋白是否呈Lewis b（Leb）、唾液酸化Lewis x（SLex）或乳糖二N-乙酰氨基葡糖（LacdiNAc）阳性，在中性与酸性pH条件下，儿科消化性溃疡病患者分离的幽门螺杆菌菌株对人及恒河猴胃黏蛋白的黏附能力均高于非溃疡性消化不良菌株。 除babA阳性菌株在消化性溃疡病相关菌株中更为常见外，在酸性pH条件下，幽门螺杆菌babA阳性菌株对胃黏蛋白的结合亲和力也高于非溃疡性消化不良babA阳性菌株。在中性pH（而非酸性pH）条件下，babA阳性消化性溃疡病幽门螺杆菌菌株对Leb的结合水平高于非溃疡性消化不良菌株。 源自消化性溃疡病的babA基因敲除突变株在酸性与中性pH条件下对黏蛋白及Leb的结合能力减弱，且在酸性pH条件下对SLex与乳糖二N-乙酰氨基葡糖的结合也受到抑制。 本研究结果凸显了BabA介导的儿科致溃疡性幽门螺杆菌菌株黏附的作用，并表明BabA在酸性pH条件下结合带电结构的功能独立于其特定的血型结合活性。