Duncan Matthew J, Li Guojie, Shin Jeoung-Sook, Carson Johnny L, Abraham Soman N
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Biol Chem. 2004 Apr 30;279(18):18944-51. doi: 10.1074/jbc.M400769200. Epub 2004 Feb 19.
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) RNA(i) 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.
1型菌毛大肠杆菌是最常见的人类尿路病原体，其大部分毒力归因于对尿路上皮的侵袭，由于尿膜蛋白和高度有序的脂质成分占优势，尿路上皮具有高度的不渗透性。我们试图通过使用人5637膀胱上皮细胞来阐明大肠杆菌侵袭膀胱上皮的分子基础，我们发现了以下几点：（i）细胞内大肠杆菌与小窝和脂筏成分相关；（ii）RNA干扰降低小窝蛋白-1的表达会抑制细菌侵袭；（iii）大肠杆菌侵袭所需的一种信号分子位于脂筏中，并与小窝蛋白-1存在物理关联；（iv）脂筏破坏/夺取剂会抑制细菌侵袭。在小鼠膀胱中，大肠杆菌1型菌毛受体尿膜蛋白Ia位于脂筏中，脂筏破坏剂会抑制大肠杆菌的侵袭。总的来说，大肠杆菌对尿路上皮的侵袭是通过脂筏发生的，而脂筏却反常地导致膀胱具有不渗透性。
