Bacterial penetration of bladder epithelium through lipid rafts
Bacterial penetration of bladder epithelium through lipid rafts
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DOI：
10.1074/jbc.m400769200
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发表时间：
2004-04-30
影响因子：
4.8
通讯作者：
Abraham, SN
中科院分区：
文献类型：
--
作者：
Duncan, MJ;Li, GJ;Abraham, SN
1型菌毛大肠埃希菌是最常见的人类尿路病原体，由于其对尿路上皮的侵袭具有很大的毒力，而由于尿路上皮的优势和高度有序的脂质成分，尿路上皮具有高度的不通透性。我们试图通过使用人5637膀胱上皮细胞来阐明大肠杆菌入侵膀胱上皮细胞的分子基础，我们发现：(I)细胞内的大肠杆菌与小窝和脂筏成分相关；(Ii)RNAi降低小窝和脂筏成分的表达抑制细菌的入侵；(Iii)大肠杆菌入侵所需的信号分子位于脂筏中并且物理上与小窝-1相关；(Iv)细菌的入侵被脂筏破坏/篡夺剂抑制。在小鼠膀胱中，大肠杆菌1型菌毛受体Uroplakin Ia位于脂筏中，而脂筏干扰物抑制了大肠杆菌的入侵。总体而言，大肠杆菌的尿路上皮细胞入侵是通过脂筏发生的，相反，脂筏导致了膀胱的不通透性。
Type 1 fimbriated Escherichia coli represents the most common human uropathogen, owing much of its virulence to invasion of the uroepithelium, which is highly impermeable due to the preponderance of uroplakins and highly ordered lipid components. We sought to elucidate the molecular basis for E. coli invasion of the bladder epithelium by employing human 5637 bladder epithelial cells, and we found the following: ( i) intracellular E. coli associated with caveolae and lipid raft components; (ii) RNAi reduction of caveolin-1 expression inhibited bacterial invasion; (iii) a signaling molecule required for E. coli invasion was located in lipid rafts and physically associated with caveolin-1; (iv) bacterial invasion was inhibited by lipid raft disrupting/ usurping agents. In the mouse bladder, the E. coli type 1 fimbrial receptor, uroplakin Ia, was located in lipid rafts, and lipid raft disruptors inhibited E. coli invasion. Cumulatively, E. coli uroepithelial invasion occurs through lipid rafts, which, paradoxically, contribute to bladder impermeability.