Liu Ai-Ning, Teng Kai-Wen, Chew Yongyu, Wang Po-Chuan, Nguyen Tram Thi Hong, Kao Mou-Chieh
Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Gastroenterology, Hsinchu MacKay Memorial Hospital, Hsinchu 30013, Taiwan.
Biomedicines. 2022 Jan 10;10(1):145. doi: 10.3390/biomedicines10010145.
infection is associated with several gastric diseases, including gastritis, peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphatic tissue (MALT) lymphoma. Due to the prevalence and severeness of infection, a thorough understanding of this pathogen is necessary. Lipopolysaccharide, one of the major virulence factors of , can exert immunomodulating and immunostimulating functions on the host. In this study, the and genes were under investigation. These two genes potentially encode GDP-D-mannose dehydratase (GMD) and phosphomannomutase (PMM)/phosphoglucomutase (PGM), respectively, and are involved in the biosynthesis of fucose. and knockout mutants were generated; both mutants displayed a truncated LPS, suggesting that the encoded enzymes are not only involved in fucose production but are also important for LPS construction. In addition, these two gene knockout mutants exhibited retarded growth, increased surface hydrophobicity and autoaggregation as well as being more sensitive to the detergent SDS and the antibiotic novobiocin. Furthermore, the LPS-defective mutants also had significantly reduced bacterial infection, adhesion and internalization in the in vitro cell line model. Moreover, disruptions of the and genes in altered protein sorting into outer membrane vesicles. The critical roles of and in LPS biosynthesis, bacterial fitness and pathogenesis make them attractive candidates for drug inventions against infection.
感染与多种胃部疾病相关，包括胃炎、消化性溃疡、胃腺癌和黏膜相关淋巴组织（MALT）淋巴瘤。由于该感染的普遍性和严重性，有必要深入了解这种病原体。脂多糖是该病原体的主要毒力因子之一，可对宿主发挥免疫调节和免疫刺激功能。在本研究中，对该病原体的两个基因进行了研究。这两个基因分别可能编码GDP-D-甘露糖脱水酶（GMD）和磷酸甘露糖变位酶（PMM）/磷酸葡萄糖变位酶（PGM），并参与岩藻糖的生物合成。构建了这两个基因的敲除突变体；两个突变体均显示出截短的脂多糖，表明所编码的酶不仅参与岩藻糖的产生，而且对脂多糖的构建也很重要。此外，这两个基因敲除突变体表现出生长迟缓、表面疏水性增加和自聚集，并且对去污剂十二烷基硫酸钠和抗生素新生霉素更敏感。此外，在体外细胞系模型中，脂多糖缺陷型突变体的细菌感染、黏附和内化也显著减少。此外，该病原体中这两个基因的破坏改变了外膜囊泡中的蛋白质分选。这两个基因在脂多糖生物合成、细菌适应性和发病机制中的关键作用使其成为抗该病原体感染药物研发的有吸引力的候选靶点。
