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探测与幽门螺杆菌感染相关糖脂的表达和黏附。

Probing the expression and adhesion of glycans involved in Helicobacter pylori infection.

机构信息

School of Science, RMIT University, Melbourne, VIC, 3000, Australia.

Department of Paediatrics, The University of Melbourne, Parkville, VIC, 3010, Australia.

出版信息

Sci Rep. 2024 Apr 13;14(1):8587. doi: 10.1038/s41598-024-59234-w.

Abstract

Helicobacter pylori infects approximately half the human population and has an unusual infective niche of the human stomach. Helicobacter pylori is a major cause of gastritis and has been classified as a group 1 carcinogen by the WHO. Treatment involves triple or quadruple antibiotic therapy, but antibiotic resistance is becoming increasingly prevalent. Helicobacter pylori expresses certain blood group related antigens (Lewis system) as a part of its lipopolysaccharide (LPS), which is thought to assist in immune evasion. Additionally, H. pylori LPS participates in adhesion to host cells alongside several adhesion proteins. This study profiled the carbohydrates of H. pylori reference strains (SS1 and 26695) using monoclonal antibodies (mAbs) and lectins, identifying interactions between two carbohydrate-targeting mAbs and multiple lectins. Atomic force microscopy (AFM) scans were used to probe lectin and antibody interactions with the bacterial surfaces. The selected mAb and lectins displayed an increased adhesive force over the surface of the curved H. pylori rods. Furthermore, this study demonstrates the ability of anti-carbohydrate antibodies to reduce the adhesion of H. pylori 26695 to human gastric adenocarcinoma cells via AFM. Targeting bacterial carbohydrates to disrupt crucial adhesion and immune evasion mechanisms represents a promising strategy for combating H. pylori infection.

摘要

幽门螺杆菌感染了大约一半的人类,其感染人类胃部的位置非常特殊。幽门螺杆菌是胃炎的主要病因之一,被世界卫生组织(WHO)列为 1 类致癌物。治疗方法涉及三联或四联抗生素疗法,但抗生素耐药性日益普遍。幽门螺杆菌在其脂多糖(LPS)中表达某些血型相关抗原(Lewis 系统),这被认为有助于免疫逃避。此外,H. pylori LPS 与多种黏附蛋白一起参与与宿主细胞的黏附。本研究使用单克隆抗体(mAb)和凝集素对幽门螺杆菌参考菌株(SS1 和 26695)的碳水化合物进行了分析,鉴定了两种针对碳水化合物的 mAb 与多种凝集素之间的相互作用。原子力显微镜(AFM)扫描用于探测凝集素和抗体与细菌表面的相互作用。选定的 mAb 和凝集素在弯曲的幽门螺杆菌杆状表面上表现出增加的粘附力。此外,本研究通过 AFM 证明了抗碳水化合物抗体能够减少幽门螺杆菌 26695 对人胃腺癌细胞的粘附。靶向细菌碳水化合物以破坏关键的黏附和免疫逃避机制,代表了一种对抗幽门螺杆菌感染的有前途的策略。

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