幽门螺杆菌是一种革兰氏阴性病原体,可以增加感染患者患胃癌的风险。幽门螺杆菌利用脂筏感染宿主细胞。感染引发Lewisx抗原(Lex)和整合素在脂筏中聚集,以促进幽门螺杆菌粘附于胃上皮。幽门螺杆菌感染可以用含有乳酸菌的益生菌治疗,所述益生菌为宿主提供许多益处,同时缺乏与抗生素治疗相关的副作用。以前,我们发现鼠李糖乳杆菌JB3(LR-JB3)来源的无细胞上清液(CFS)在感染复数(MOI)为25时减弱了幽门螺杆菌的致病性。在这项研究中,我们建立了一个黏蛋白模型来模拟胃环境,进一步了解黏蛋白对幽门螺杆菌发病机制的影响。猪胃粘蛋白显著上调幽门螺杆菌毒力基因表达,包括巴巴的,saba,他妈的,vaca,hp0499,cagA,还有cagl,以及幽门螺杆菌的粘附和侵袭能力,并诱导感染的AGS细胞中IL-8水平升高。来自LR-JB3的CFS在MOI为25时降低了幽门螺杆菌sabA的表达,他妈的,和粘蛋白中的HP0499,以及共培养过程中AGS细胞中的Lex抗原和α5β1整联蛋白。LR-JB3的这些抑制作用还抑制了脂筏聚集并减弱了Lewis抗原依赖性粘附,IV型分泌系统介导的细胞接触,和脂质筏介导的VacA进入宿主细胞。总之,LR-JB3可能通过介导宿主细胞的脂筏形成来影响幽门螺杆菌感染。从LR-JB3分泌的目前未知的线索不仅是有价值的治疗幽门螺杆菌感染,而且用于治疗也由脂筏信号介导的疾病,如癌症和衰老相关和神经退行性疾病。
Helicobacter pylori is a Gram-negative pathogen that can increase the risk of stomach cancer in infected patients. H. pylori exploits lipid rafts to infect host cells. Infection triggers clustering of Lewis x antigen (Lex) and integrins in lipid rafts to facilitate H. pylori adherence to the gastric epithelium. H. pylori infection can be treated with probiotics containing lactic acid bacteria that offer numerous benefits to the host while lacking the side effects associated with antibiotic therapy. Previously, we showed that the cell-free supernatant (CFS) derived from Lactobacillus rhamnosus JB3 (LR-JB3) at a multiplicity of infection (MOI) of 25 attenuated the pathogenicity of H. pylori. In this study, we established a mucin model to simulate the gastric environment and to further understand the influence of mucin on the pathogenesis of H. pylori. Porcine stomach mucin dramatically upregulated H. pylori virulence gene expression, including that of babA, sabA, fucT, vacA, hp0499, cagA, and cagL, as well as the adhesion and invasion ability of H. pylori and induced increased levels of IL-8 in infected-AGS cells. The CFS derived from LR-JB3 at a MOI of 25 reduced the expression of H. pylori sabA, fucT, and hp0499 in mucin, as well as that of the Lex antigen and the α5β1 integrin in AGS cells during co-cultivation. These inhibitory effects of LR-JB3 also suppressed lipid raft clustering and attenuated Lewis antigen-dependent adherence, type IV secretion system-mediated cell contact, and lipid raft-mediated entry of VacA to host cells. In conclusion, LR-JB3 could affect H. pylori infection through mediating lipid raft formation of the host cells. The currently unknown cues secreted from LR-JB3 are valuable not only for treating H. pylori infection, but also for treating diseases that are also mediated by lipid raft signaling, such as cancer and aging-associated and neurodegenerative conditions.