Chitin-binding domains of Escherichia coli ChiA mediate interactions with intestinal epithelial cells in mice with colitis.
Chitin-binding domains of Escherichia coli ChiA mediate interactions with intestinal epithelial cells in mice with colitis.
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DOI：
10.1053/j.gastro.2013.05.017
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发表时间：
2013-09
期刊：
影响因子：
29.4
通讯作者：
Mizoguchi E
中科院分区：
文献类型：
--
作者：
Low D;Tran HT;Lee IA;Dreux N;Kamba A;Reinecker HC;Darfeuille-Michaud A;Barnich N;Mizoguchi E
诱导型几丁质酶 3-like-1 (CHI3L1) 由肠上皮细胞 (IEC) 表达，并在炎症条件下粘附在细菌上。我们对 chiA 基因编码的几丁质结合域 (CBD) 进行了结构-功能分析，该基因介导粘附侵袭性大肠杆菌 (AIEC) 的致病作用。我们创建了缺失 chiA (LF82-ΔchiA) 或表达具有特定突变的 chiA 的 AIEC（菌株 LF82）。我们研究了这些细菌感染不同 IEC 系的效果，并与非致病性大肠杆菌进行了比较；使用胶体几丁质天蓝色法测量几丁质酶活性。通过给予葡聚糖硫酸钠(DSS)诱导C57/Bl6小鼠结肠炎，并通过连续15天给小鼠灌胃108种细菌。收集并分析粪便/组织样本。 LF82-ΔchiA 对 IEC 线的粘附力明显低于 LF82。 LF82-ΔchiA 与 LF82 chiA 基因互补，但不与非致病性 (K12) 大肠杆菌中的 chiA 互补，可增加粘附力。我们在 LF82 ChiA 的 CBD（氨基酸 362、370、378、388 和 548）中鉴定出 5 个特定的多态性，这些多态性与 K12 的 chiA 不同，并且是 LF82 与 IEC 直接相互作用所必需的。这种相互作用是由 IEC 上的 CHI3L1（氨基酸 68）中的 N-糖基化天冬酰胺介导的。感染 LF82 或与 LF82 chiA 互补的 LF82-ΔchiA 的小鼠在给予 DSS 后，比感染表达突变型 chiA 的 LF82-ΔchiA 或 LF82 的小鼠出现更严重的结肠炎。 AIEC 通过 chiA 的 CBD 遵守 IEC 上的 N-糖基化 CHI3L1。这种机制促进了 AIEC 对结肠炎小鼠的致病作用。
Inducible chitinase 3-like-1 (CHI3L1) is expressed by intestinal epithelial cells (IECs) and adheres to bacteria under conditions of inflammation. We performed a structure–function analysis of the chitin-binding domains (CBDs) encoded by the chiA gene, which mediates the pathogenic effects of adherent invasive Escherichia coli (AIEC). We created AIEC (strain LF82) with deletion of chiA (LF82-ΔchiA) or that expressed chiA with specific mutations. We investigated the effects of infecting different IEC lines with these bacteria, compared with non-pathogenic E coli; chitinase activities were measured using the colloidal chitin-azure method. Colitis was induced in C57/Bl6 mice by administration of dextran sodium sulfate (DSS), and mice were given 108 bacteria for 15 consecutive days by gavage. Stool/tissue samples were collected and analyzed. LF82-ΔchiA had significantly less adhesion to IEC lines than LF82. Complementation of LF82-ΔchiA with the LF82 chiA gene, but not chiA from non-pathogenic (K12) E coli, increased adhesion. We identified 5 specific polymorphisms in the CBD of LF82 ChiA (at amino acids 362, 370, 378, 388, and 548) that differ from chiA of K12 and were required for LF82 to interact directly with IECs. This interaction was mediated by an N-glycosylated asparagine in CHI3L1 (amino acid 68) on IECs. Mice infected with LF82, or LF82-ΔchiA complemented with LF82 chiA, developed more severe colitis following administration of DSS than mice infected with LF82-ΔchiA or LF82 that expressed mutant forms of chiA. AIEC adhere to an N-glycosylated CHI3L1 on IEC via the CBD of chiA. This mechanism of promotes pathogenic effects of AIEC in mice with colitis.
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