Solnick Jay V, Hansen Lori M, Salama Nina R, Boonjakuakul Jenni K, Syvanen Michael
Departments of Medicine and Medical Microbiology and Immunology, and Center for Comparative Medicine, University of California, Davis, CA 95616.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2106-11. doi: 10.1073/pnas.0308573100. Epub 2004 Feb 3.
Clinical isolates of Helicobacter pylori show marked diversity, which may derive from genomic changes that occur during the often lifelong association of the bacterium with its human host. We used the rhesus macaque model, together with DNA microarrays, to examine genomic changes in H. pylori that occur early during experimental infection. Microarray analysis showed that H. pylori recovered from challenged macaques had deleted babA, a member of a large family of paralogous outer membrane proteins (OMPs) that mediates attachment of H. pylori to the Lewis B blood group antigen on gastric epithelium. In some cases the babA gene was replaced by babB, an uncharacterized OMP that is closely related to babA. In other cases the babA gene was present but was not expressed because of alteration in dinucleotide CT repeats in the 5' coding region. In either case, strains lacking babA did not adhere to Lewis B, which is expressed on macaque gastric epithelium. Absence of babA and duplication of babB was also seen in H. pylori isolates derived from human clinical samples, suggesting that this gene conversion event is not unique to experimentally infected rhesus monkeys. These results demonstrate in real time with a relevant animal model that H. pylori regulates OMP expression in vivo by using both antigenic variation and phase variation. We suggest that changes in babA and babB after experimental infection of macaques represent a dynamic response in the H. pylori outer membrane that facilitates adherence to the gastric epithelium and promotes chronic infection.
幽门螺杆菌的临床分离株表现出显著的多样性，这可能源于该细菌在与其人类宿主通常长达一生的关联过程中发生的基因组变化。我们使用恒河猴模型以及DNA微阵列，来研究实验性感染早期幽门螺杆菌发生的基因组变化。微阵列分析显示，从受攻击的猕猴体内分离出的幽门螺杆菌缺失了babA基因，babA是一大类同源外膜蛋白（OMPs）家族的成员，介导幽门螺杆菌与胃上皮细胞上的Lewis B血型抗原的附着。在某些情况下，babA基因被babB取代，babB是一种与babA密切相关但功能未明的OMP。在其他情况下，babA基因存在，但由于5'编码区二核苷酸CT重复序列的改变而未表达。无论哪种情况，缺乏babA的菌株都不黏附于猕猴胃上皮细胞上表达的Lewis B抗原。在源自人类临床样本的幽门螺杆菌分离株中也观察到了babA的缺失和babB的重复，这表明这种基因转换事件并非实验性感染的恒河猴所特有。这些结果通过一个相关的动物模型实时证明，幽门螺杆菌通过抗原变异和相变在体内调节OMP的表达。我们认为，猕猴实验性感染后babA和babB的变化代表了幽门螺杆菌外膜的一种动态反应，有助于黏附于胃上皮细胞并促进慢性感染。
