Censini S, Lange C, Xiang Z, Crabtree J E, Ghiara P, Borodovsky M, Rappuoli R, Covacci A
Immunobiological Research Institute of Siena, Chiron Vaccines, Italy.
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14648-53. doi: 10.1073/pnas.93.25.14648.
cagA, a gene that codes for an immunodominant antigen, is present only in Helicobacter pylori strains that are associated with severe forms of gastroduodenal disease (type I strains). We found that the genetic locus that contains cagA (cag) is part of a 40-kb DNA insertion that likely was acquired horizontally and integrated into the chromosomal glutamate racemase gene. This pathogenicity island is flanked by direct repeats of 31 bp. In some strains, cag is split into a right segment (cagI) and a left segment (cagII) by a novel insertion sequence (IS605). In a minority of H. pylori strains, cagI and cagII are separated by an intervening chromosomal sequence. Nucleotide sequencing of the 23,508 base pairs that form the cagI region and the extreme 3' end of the cagII region reveals the presence of 19 ORFs that code for proteins predicted to be mostly membrane associated with one gene (cagE), which is similar to the toxin-secretion gene of Bordetella pertussis, ptlC, and the transport systems required for plasmid transfer, including the virB4 gene of Agrobacterium tumefaciens. Transposon inactivation of several of the cagI genes abolishes induction of IL-8 expression in gastric epithelial cell lines. Thus, we believe the cag region may encode a novel H. pylori secretion system for the export of virulence determinants.
cagA基因编码一种免疫显性抗原，仅存在于与严重形式的胃十二指肠疾病相关的幽门螺杆菌菌株（I型菌株）中。我们发现，包含cagA的基因座（cag）是一个40kb DNA插入片段的一部分，该片段可能是水平获得并整合到染色体谷氨酸消旋酶基因中的。这个致病岛两侧是31bp的直接重复序列。在一些菌株中，cag被一个新的插入序列（IS605）分成一个右片段（cagI）和一个左片段（cagII）。在少数幽门螺杆菌菌株中，cagI和cagII被一个中间染色体序列隔开。对构成cagI区域和cagII区域最末端3'端的23508个碱基对进行核苷酸测序，发现存在19个开放阅读框，这些开放阅读框编码的蛋白质预计大多与膜相关，其中一个基因（cagE）与百日咳博德特氏菌的毒素分泌基因ptlC以及质粒转移所需的转运系统相似，包括根癌土壤杆菌的virB4基因。对几个cagI基因进行转座子失活可消除胃上皮细胞系中IL-8表达的诱导。因此，我们认为cag区域可能编码一种新型的幽门螺杆菌分泌系统，用于输出毒力决定因素。
