Wirth H P, Beins M H, Yang M, Tham K T, Blaser M J
Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2605, USA.
Infect Immun. 1998 Oct;66(10):4856-66. doi: 10.1128/IAI.66.10.4856-4866.1998.
Experimental Helicobacter pylori infection was studied in Mongolian gerbils with fresh human isolates that carry or do not carry cagA (cagA-positive or cagA-negative, respectively), multiply passaged laboratory strains, wild-type strain G1.1, or isogenic ureA, cagA, or vacA mutants of G1.1. Animals were sacrificed 1 to 32 weeks after challenge, the stomach was removed from each animal for quantitative culture, urease test, and histologic testing, and blood was collected for antibody determinations. No colonization occurred after >/=20 in vitro passages of wild-type strain G1.1 or with the ureA mutant of G1.1. In contrast, infection occurred in animals challenged with wild-type G1.1 (99 of 101 animals) or the cagA (25 of 25) or vacA (25 of 29) mutant of G1.1. Infection with G1.1 persisted for at least 8 months. All 15 animals challenged with any of three fresh human cagA-positive isolates became infected, in contrast to only 6 (23%) of 26 animals challenged with one of four fresh human cagA-negative isolates (P < 0.001). Similar to infection in humans, H. pylori colonization of gerbils induced gastric inflammation and a systemic antibody response to H. pylori antigens. These data confirm the utility of gerbils as an animal model of H. pylori infection and indicate the importance of bacterial strain characteristics for successful infection.
利用携带或不携带cagA(分别为cagA阳性或cagA阴性)的新鲜人分离株、多次传代的实验室菌株、野生型菌株G1.1或G1.1的等基因ureA、cagA或vacA突变体,对蒙古沙鼠进行实验性幽门螺杆菌感染研究。在攻击后1至32周处死动物,从每只动物身上取出胃进行定量培养、尿素酶试验和组织学检测,并采集血液进行抗体测定。野生型菌株G1.1或G1.1的ureA突变体在体外传代≥20次后未发生定植。相比之下,用野生型G1.1(101只动物中的99只)或G1.1的cagA(25只中的25只)或vacA(29只中的25只)突变体攻击的动物发生了感染。用G1.1感染持续了至少8个月。用三种新鲜人cagA阳性分离株中的任何一种攻击的所有15只动物都被感染,相比之下,用四种新鲜人cagA阴性分离株中的一种攻击的26只动物中只有6只(23%)被感染(P<0.001)。与人类感染相似,沙鼠幽门螺杆菌定植诱导了胃炎症和对幽门螺杆菌抗原的全身性抗体反应。这些数据证实了沙鼠作为幽门螺杆菌感染动物模型的实用性,并表明细菌菌株特征对成功感染的重要性。