TYROSINE PROTEIN-KINASE INHIBITORS BLOCK INVASION-PROMOTED BACTERIAL UPTAKE BY EPITHELIAL-CELLS
TYROSINE PROTEIN-KINASE INHIBITORS BLOCK INVASION-PROMOTED BACTERIAL UPTAKE BY EPITHELIAL-CELLS
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DOI：
10.1128/iai.60.6.2211-2217.1992
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发表时间：
1992-06-01
影响因子：
3.1
通讯作者：
FINLAY, BB
中科院分区：
文献类型：
--
作者：
ROSENSHINE, I;DURONIO, V;FINLAY, BB
进入（侵入）哺乳动物细胞的能力是许多致病细菌和细胞内寄生虫的重要毒力决定因素。 这些生物体在附着于其表面时被宿主细胞内化。 然而，细胞内寄生虫诱导内化到宿主细胞中的机制尚未确定。 我们发现蛋白激酶抑制剂星形孢菌素可以阻断一些致病菌的侵袭，包括小肠结肠炎耶尔森菌和假结核耶尔森菌。 利用含有克隆的Y.通过对小肠结肠炎侵袭基因inv（其编码侵袭素，一种整合素结合蛋白）的研究，我们发现星形孢菌素通过阻断细菌内化来抑制侵袭。 两个特定的酪氨酸蛋白激酶抑制剂，染料木黄酮和tyrphostin，也阻止内化，但不结合的细菌，这表明细菌的摄取可能依赖于这种酶类在宿主HeLa细胞的活性。 与入侵促进的入侵相反，鼠伤寒沙门氏菌对HeLa细胞的入侵不受任何这些药物的抑制。
The ability to enter into (invade) mammalian cells is an essential virulence determinant of many pathogenic bacteria and intracellular parasites. These organisms are internalized by host cells upon attachment to their surface. However, the mechanisms used by intracellular parasites to induce internalization into host cells have not been defined. We found that the protein kinase inhibitor staurosporine blocks invasion by some pathogenic bacteria, including Yersinia enterocolitica and Yersinia pseudotuberculosis. Using Escherichia coli containing the cloned Y. enterocolitica invasion gene inv (which codes for invasin, an integrin-binding protein), we found that staurosporine inhibits invasion by blocking bacterial internalization. Two specific tyrosine protein kinase inhibitors, genistein and tyrphostin, also block the internalization but not the binding of bacteria, suggesting that bacterial uptake may be dependent on the activity of this enzyme class in host HeLa cells. In contrast to invasion promoted by invasion, the invasion of HeLa cells by Salmonella typhimurium is not inhibited by any of these drugs.