Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques
Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques
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DOI：
10.1073/pnas.0308573100
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发表时间：
2004-02-17
影响因子：
11.1
通讯作者：
Syvanen, M
中科院分区：
文献类型：
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作者：
Solnick, JV;Hansen, LM;Syvanen, M
幽门螺杆菌的临床分离株表现出显着的多样性，这可能源于细菌与其人类宿主终生交往期间发生的基因组变化。我们使用恒河猴模型和 DNA 微阵列来检查实验感染早期发生的幽门螺杆菌基因组变化。微阵列分析表明，从受攻击的猕猴中回收的幽门螺杆菌已删除了 babA，babA 是旁系同源外膜蛋白 (OMP) 大家族的成员，可介导幽门螺杆菌与胃上皮上 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 密切相关的未表征的 OMP。在其他情况下，babA 基因存在，但由于 5' 编码区中二核苷酸 CT 重复的改变而未表达。在这两种情况下，缺乏 babA 的菌株都不会粘附在猕猴胃上皮上表达的 Lewis B。在源自人类临床样本的幽门螺杆菌分离物中也发现了 babA 的缺失和 babB 的重复，这表明这种基因转换事件并非实验感染的恒河猴所独有。这些结果通过相关动物模型实时证明，幽门螺杆菌通过使用抗原变异和相位变异来调节体内 OMP 表达。我们认为，猕猴实验感染后 babA 和 babB 的变化代表了幽门螺杆菌外膜的动态反应，有利于粘附到胃上皮并促进慢性感染。
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.