Guruge J L, Falk P G, Lorenz R G, Dans M, Wirth H P, Blaser M J, Berg D E, Gordon J I
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3925-30. doi: 10.1073/pnas.95.7.3925.
Genetically defined in vivo models are needed to assess the importance of target cell attachment in bacterial pathogenesis. Gastric colonization by Helicobacter pylori in human populations is common and persistent, and has various outcomes including peptic ulcers and cancer. The impact of attachment on the course of infection was examined in transgenic mice expressing a human receptor for H. pylori in their gastric epithelium. Persistent infection by a clinical isolate occurred at comparable microbial densities in transgenic and nontransgenic littermates. However, microbial attachment in transgenic mice resulted in production of autoantibodies to Lewisx carbohydrate epitopes shared by bacteria and acid-secreting parietal cells, chronic gastritis, and parietal cell loss. This model should help identify bacterial and host genes that produce attachment-related pathology.
需要通过基因定义的体内模型来评估靶细胞附着在细菌致病过程中的重要性。幽门螺杆菌在人群中的胃部定植常见且持续存在,会产生包括消化性溃疡和癌症在内的多种后果。在胃上皮中表达人幽门螺杆菌受体的转基因小鼠中,研究了附着对感染进程的影响。临床分离株在转基因和非转基因同窝小鼠中以相当的微生物密度引发持续感染。然而,转基因小鼠中的微生物附着导致产生针对细菌和分泌酸的壁细胞共有的Lewisx碳水化合物表位的自身抗体、慢性胃炎和壁细胞损失。该模型应有助于识别产生与附着相关病理的细菌和宿主基因。