Department of Pharmacy, University of Salerno, 84084 Fisciano (SA), Italy.
PhD Program in Drug Discovery and Development, University of Salerno, 84084 Fisciano (SA), Italy.
Int J Mol Sci. 2021 Feb 12;22(4):1851. doi: 10.3390/ijms22041851.
Gastric cancer is considered one of the most common malignancies in humans and infection is the major environmental risk factor of gastric cancer development. Given the high spread of this bacterium whose infection is mostly asymptomatic, colonization persists for a long time, becoming chronic and predisposing to malignant transformation. The first defensive barrier from bacterial infection is constituted by the gastric mucosa that secretes several protective factors, among which is the trefoil factor 1 (TFF1), that, as mucin 5AC, binds the bacterium. Even if the protective role of TFF1 is well-documented, the molecular mechanisms that confer a beneficial function to the interaction among TFF1 and remain still unclear. Here we analyze the effects of this interaction on at morphological and molecular levels by means of microscopic observation, chemiotaxis and motility assays and real-time PCR analysis. Our results show that TFF1 favors aggregation of and significantly slows down the motility of the bacterium across the mucus. Such aggregates significantly reduce both and gene transcription compared with bacteria not incubated with TFF1. Finally, our results suggest that the interaction between TFF1 and the bacterium may explain the frequent persistence of in the human host without inducing disease.
胃癌被认为是人类最常见的恶性肿瘤之一，感染是胃癌发展的主要环境风险因素。由于这种细菌的传播范围很广，其感染大多无症状，定植持续时间长，成为慢性，并易发生恶性转化。抵抗细菌感染的第一道防线是胃黏膜，它分泌几种保护因子，其中包括三叶因子 1（TFF1），它像黏蛋白 5AC 一样，与细菌结合。尽管 TFF1 的保护作用已有充分的记录，但赋予 TFF1 与 相互作用有益功能的分子机制仍不清楚。在这里，我们通过显微镜观察、趋化性和运动性测定以及实时 PCR 分析，在形态和分子水平上分析了这种相互作用对 的影响。我们的结果表明，TFF1 促进 的聚集，并显著减缓细菌穿过黏液的运动。与未与 TFF1 孵育的细菌相比，这种聚集体显著降低了 和 基因的转录。最后，我们的结果表明，TFF1 与细菌的相互作用可能解释了为什么这种细菌经常在人类宿主中持续存在而不引起疾病。
