McGee D J, Mobley H L
University of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, Maryland 21201, USA.
Curr Opin Gastroenterol. 2000 Jan;16(1):24-31. doi: 10.1097/00001574-200001000-00005.
Helicobacter pylori, a gram-negative, microaerophilic, motile, spiral-shaped bacterium, has been established as the etiologic agent of gastritis and peptic ulcers and is a major risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma (MALT). The ability of H. pylori to cause this spectrum of diseases depends on host, bacterial, and environmental factors. Bacterial factors critical for H. pylori colonization of the gastric mucosa include urease, flagella, adhesins, and delta-glutamyltranspeptidase. Lipopolysaccharide, urease, and vacuolating cytotoxin are among the factors that allow H. pylori to persist for decades and invoke an intense inflammatory response, leading to damaged host cells. Genes in the cag pathogenicity island also contribute to the inflammatory response by initiating a signal transduction cascade, resulting in interleukin-8 production. Proinflammatory cytokines and a Th-1 cytokine response further exacerbates the inflammation. Products of the enzymes nitric oxide synthase (iNOS) and cyclooxygenase may perturb the balance between gastric epithelial cell apoptosis (ulcer formation) and proliferation (cancer). The host Th-1 response and antibodies directed against H. pylori do not eliminate the organism, which presents challenges to vaccine development. Vaccines that include urease have shown some promise, but improved adjuvants and animal models should hasten progress in vaccine research. H. pylori is the most genetically diverse organism known, and the panmictic population structure may contribute to the varying ranges of disease severity produced by different strains. The complete genome sequence of two strains of H. pylori has propelled this field forward, and numerous groups are now using genomic, proteomic, and mutagenetic approaches to identify new virulence genes. Discovered only in 1982, H. pylori is now among the most intensely investigated organisms. This review summarizes recent progress in this rapidly moving field.
幽门螺杆菌是一种革兰氏阴性、微需氧、具运动性的螺旋形细菌，已被确认为胃炎和消化性溃疡的病原体，也是胃腺癌和黏膜相关淋巴组织淋巴瘤（MALT）的主要危险因素。幽门螺杆菌引发这类疾病的能力取决于宿主、细菌和环境因素。对幽门螺杆菌在胃黏膜定植至关重要的细菌因素包括尿素酶、鞭毛、黏附素和δ-谷氨酰转肽酶。脂多糖、尿素酶和空泡毒素是使幽门螺杆菌能够持续数十年并引发强烈炎症反应、导致宿主细胞受损的因素。cag致病岛中的基因也通过启动信号转导级联反应，促使白细胞介素-8产生，从而促进炎症反应。促炎细胞因子和Th-1细胞因子反应会进一步加剧炎症。一氧化氮合酶（iNOS）和环氧化酶的产物可能会扰乱胃上皮细胞凋亡（溃疡形成）和增殖（癌症）之间的平衡。宿主的Th-1反应以及针对幽门螺杆菌的抗体并不能清除该病原体，这给疫苗研发带来了挑战。包含尿素酶的疫苗已显示出一定前景，但改进佐剂和动物模型应能加快疫苗研究的进展。幽门螺杆菌是已知基因多样性最高的生物体，随机交配群体结构可能导致不同菌株引发的疾病严重程度范围各异。两株幽门螺杆菌的全基因组序列推动了该领域的发展，现在许多研究团队正在使用基因组学、蛋白质组学和诱变方法来鉴定新的毒力基因。幽门螺杆菌直到1982年才被发现，如今它已成为研究最为深入的生物体之一。本综述总结了这个快速发展领域的最新进展。
