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首页> 外文期刊>Comparative Medicine >Genotoxic Escherichia coli Strains Encoding Colibactin, Cytolethal Distending Toxin, and Cytotoxic Necrotizing Factor in Laboratory Rats
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Genotoxic Escherichia coli Strains Encoding Colibactin, Cytolethal Distending Toxin, and Cytotoxic Necrotizing Factor in Laboratory Rats

机译：编码Colibactin，细胞素脱光毒素和实验室大鼠细胞毒性坏死因子的基因毒性大肠杆菌菌株

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摘要

Although many Escherichia coli strains are considered commensals in mammals, strains encoding the cyclomodulin genotoxins are associated with clinical and subclinical disease in the urogenital and gastrointestinal tracts, meningitis, and inflammatory disorders. These genotoxins include the polyketide synthase (pks) pathogenicity island, cytolethal distending toxin (cdt), and hemolysin-associated cytotoxic necrotizing factor (cnf). E. coli strains are not excluded from rodents housed under SPF conditions in academic or vendor facilities. This study isolated and characterized genotoxin-encoding E. coli from laboratory rats obtained from 4 academic institutions and 3 vendors. A total of 69 distinct E. coli isolates were cultured from feces, rectal swab, nares, or vaginal swab of 52 rats and characterized biochemically. PCR analysis for cyclomodulin genes and phylogroup was performed on all 69 isolates. Of the 69 isolates, 45 (65%) were positive for pks, 20/69 (29%) were positive for cdt, and 4 (6%) were positive for cnf. Colibactin was the sole genotoxin identified in 21 of 45 pks(+) isolates (47%), whereas cdt or cnf was also present in the remaining 24 isolates (53%); cdt and cnf were never present together or without pks. All genotoxin-associated strains were members of pathogen-associated phylogroup B2. Fisher exact and chi(2) tests demonstrated significant differences in genotoxin prevalence and API code distribution with regard to vendor. Select E. coli isolates were characterized by HeLa cell in vitro cytotoxicity assays, serotyped, and whole-genome sequenced. All isolates encoding cyclomodulins induced megalocytosis. Serotypes corresponded with vendor origin and cyclomodulin composition, with the cnf(+) serotype representing a known human uropathogen. Whole-genome sequencing confirmed the presence of complete pks, cdt, and hemolysin-cnf pathogenicity islands. These findings indicate that genotoxin-encoding E. coli colonize laboratory rats from multiple commercial vendors and academic institutions and suggest the potential to contribute to clinical disease and introduce confounding variables into experimental rat models.
机译：尽管许多大肠杆菌菌株被认为是哺乳动物中的共生，但编码环偶毒素遗传毒素的菌株与泌尿生殖器和胃肠道，脑膜炎和炎症性疾病中的临床和亚临床疾病有关。这些基因毒素包括聚酮合成酶（PKS）致病性岛，细胞骨偏移毒素（CDT）和血谷素相关的细胞毒性坏死因子（CNF）。大肠杆菌菌株不会排除在学术或供应商设施的SPF条件下的啮齿动物中。本研究分离和表征从4个学术机构和3个供应商获得的实验室大鼠的遗传毒素编码大肠杆菌。从粪便，直肠拭子，沥青或阴道拭子培养了总共69种不同的大肠杆菌分离物，并在52大鼠的阴道拭子中培养并表征生物化学。对所有69个分离株进行环瘤阳蛋白基因和晶粒的PCR分析。在69个分离物中，45（65％）为PKS阳性，20/69（29％）对于CDT阳性，4（6％）为CNF阳性。 CoIbactin是在41种（+）分离株（47％）中鉴定的唯一遗传毒素，而CDT或CNF也存在于剩余的24个分离物中（53％）; CDT和CNF永远不会在一起或没有PKS呈现。所有基因毒素相关的菌株是病原体相关的植物群B2的成员。 Fisher精确和Chi（2）测试表现出对供应商的遗传毒素流行和API代码分配的显着差异。选择大肠杆菌分离物的特征在于Hela细胞体外细胞毒性测定，血清型和全基因组测序。所有分离株编码环瘤仲裁蛋白诱导肿瘤症。血清型与供应商来源和环瘤组合物相对应，CNF（+）血清型代表已知的人尿胆肠。全基因组测序证实了完整的PKS，CDT和血溶酪素-CNF致病性岛的存在。这些发现表明，从多个商业供应商和学术机构的遗传毒素编码大肠杆菌殖民大鼠，并提出了促进临床疾病的潜力，并将混淆变量引入实验性大鼠模型中。

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