Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer.
Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer.
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DOI：
10.1136/gutjnl-2013-304739
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发表时间：
2014-05
期刊：
影响因子：
24.5
通讯作者：
Campbell BJ
中科院分区：
文献类型：
--
作者：
Prorok-Hamon M;Friswell MK;Alswied A;Roberts CL;Song F;Flanagan PK;Knight P;Codling C;Marchesi JR;Winstanley C;Hall N;Rhodes JM;Campbell BJ
克罗恩病（CD）和结直肠癌（CRC）中结肠粘膜相关大肠杆菌增加。它们以各种方式血凝，侵入上皮细胞系，在巨噬细胞内复制，跨M（微折叠）细胞易位和损伤DNA。我们研究了负责这些影响的基因及其在结肠粘膜分离株中的共同关联。在大肠杆菌EPI 300-T1中使用来自血凝性CRC分离株的DNA制备产生968个克隆的fosmid文库，并对所得血凝性克隆进行454焦磷酸测序。对来自炎症性肠病（IBD）（35例）、CRC（21例）和对照组（24例;散发性息肉或肠易激综合征）的281株结肠大肠杆菌分离株进行PCR筛查。454-来自血凝克隆的磷酶焦磷酸测序（n=8）鉴定了无菌毛粘附素afa-1操纵子。afa-1转染到大肠杆菌K-12可预见地赋予弥漫性粘附加上HEp-2和I-407上皮细胞的侵袭，以及血管内皮生长因子的上调。大肠埃希菌表达afaC常见于CRC（14/21，p=0.0009）和CD（9/14，p=0.005），但与对照组（4/24）相比，溃疡性结肠炎（UC; 8/21）则不常见。与对照组（2/24）相比，表达afaC和lpfA（与M细胞易位相关）的大肠杆菌在CD（8/14，p=0.0019）和CRC（14/21，p=0.0001）中常见，但在UC（6/21）中不常见。大肠埃希菌同时表达afaC和pks（遗传毒性）在CRC（11/21，p=0.0015）和UC（8/21，p=0.022）中很常见，但与对照组（2/24）相比，CD（4/14）中不常见。所有分离株均表达与巨噬细胞内复制相关的dsbA和htrA，242/281株表达编码1型菌毛粘附素的fimH。IBD和CRC通常具有结肠粘膜大肠杆菌，其表达赋予与发病机制相关的特性的基因，包括M细胞易位、血管生成和遗传毒性。
Colonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates. A fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome). 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin. IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.