结肠癌相关的B2大肠杆菌定殖于肠道黏膜并促进细胞增殖。
Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation.
作者信息
Raisch Jennifer, Buc Emmanuel, Bonnet Mathilde, Sauvanet Pierre, Vazeille Emilie, de Vallée Amélie, Déchelotte Pierre, Darcha Claude, Pezet Denis, Bonnet Richard, Bringer Marie-Agnès, Darfeuille-Michaud Arlette
机构信息
Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
出版信息
World J Gastroenterol. 2014 Jun 7;20(21):6560-72. doi: 10.3748/wjg.v20.i21.6560.
AIM
To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.
METHODS
Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E. coli from colon cancer and diverticulosis specimens were determined by PCR. Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot. Gut colonization, inflammation and pro-carcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice. Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67.
RESULTS
Analysis of mucosa-associated E. coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E. coli strains, 86% of cyclomodulin-positive E. coli belonged to B2 phylogroup and most harbored polyketide synthase (pks) island, which encodes colibactin, and/or cytotoxic necrotizing factor (cnf) genes. In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E. coli strains were poorly adherent and invasive. However, mucosa-associated B2 E. coli similarly to Crohn's disease-associated E. coli are able to induce CEACAM6 expression in T84 intestinal epithelial cells. In addition, in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E. coli strain 11G5 isolated from colon cancer is able to highly persist in the gut, and to induce colon inflammation, epithelial damages and cell proliferation.
CONCLUSION
In conclusion, these data bring new insights into the ability of E. coli isolated from patients with colon cancer to establish persistent colonization, exacerbate inflammation and trigger carcinogenesis.
目的
进一步深入了解从癌症患者结肠黏膜分离出的黏膜相关大肠杆菌（E. coli）的特征。
方法
通过聚合酶链反应（PCR）确定来自结肠癌和憩室病标本的黏膜相关大肠杆菌的系统发育群以及环调节蛋白编码基因的存在情况。使用庆大霉素保护试验，对I - 407肠上皮细胞进行黏附和侵袭实验。通过酶联免疫吸附测定和蛋白质印迹法检测T84肠上皮细胞中癌胚抗原相关细胞黏附分子6（CEACAM6）的表达。在使用CEABAC10转基因小鼠的慢性感染模型中评估肠道定植、炎症和促癌潜力。通过PCNA的实时mRNA定量分析和Ki67的免疫组织化学染色分析细胞增殖情况。
结果
对来自结肠癌和憩室病标本的黏膜相关大肠杆菌的分析表明，无论大肠杆菌菌株的来源如何，86%的环调节蛋白阳性大肠杆菌属于B2系统发育群，且大多数携带编码大肠杆菌素的聚酮合酶（pks）岛和/或细胞毒性坏死因子（cnf）基因。使用I - 407肠上皮细胞进行的体外试验表明，黏膜相关B2大肠杆菌菌株的黏附和侵袭能力较差。然而，与克罗恩病相关的大肠杆菌类似，黏膜相关B2大肠杆菌能够在T84肠上皮细胞中诱导CEACAM6表达。此外，使用表达CEACAM6的小鼠的慢性感染模型进行的体内实验表明，从结肠癌分离出的B2大肠杆菌菌株11G5能够在肠道中高度持续存在，并诱导结肠炎症、上皮损伤和细胞增殖。
结论
总之，这些数据为从结肠癌患者分离出的大肠杆菌建立持续定植、加剧炎症和引发癌变的能力带来了新的见解。
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