cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors

cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors
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DOI:
10.1073/pnas.93.25.14648
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发表时间:
1996-12-10
影响因子:
11.1
通讯作者:
Covacci, A
Covacci, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Censini, S;Lange, C;Covacci, A

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CAGA是一种代码为免疫主导抗原的基因,仅存在于幽门螺杆菌菌株中,这些菌株与严重形式的胃肠道疾病(I型菌株)相关。我们发现,包含CAGA(CAG)的遗传基因座是40 kb DNA插入的一部分,该插入可能是水平获取并整合到染色体谷氨酸种族友酶基因中的40 kb DNA插入的一部分。该致病性岛的两侧是直接重复的31 bp。在某些菌株中,CAG通过新颖的插入序列(IS605)分为右段(CAGI)和左节(CAGII)。在少数幽门螺杆菌菌株中,CAGI和CAGII通过中间的染色体序列分开。形成CAGI区域的23,508碱基对核苷酸测序和CAGII区域的极端3'末端揭示了19个ORF的存在,该ORF的存在,该ORF代码为预测的蛋白质代码,预测是与一个基因相关的膜(cage),这类似于一个基因(CAG) Bordetella百日咳,PTLC和质粒转移所需的传输系统(包括农杆菌Tumefaciens的ViRB4基因)的毒素 - 分泌基因。几种CAGI基因的转座子失活废除了胃上皮细胞系中IL-8表达的诱导。因此,我们认为CAG区域可能会编码一种新型的幽门螺杆菌分泌系统,以导出毒力决定因素。
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.