Type 1 pilus-mediated bacterial invasion of bladder epithelial cells
Type 1 pilus-mediated bacterial invasion of bladder epithelial cells
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DOI：
10.1093/emboj/19.12.2803
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发表时间：
2000-06-15
期刊：
影响因子：
11.4
通讯作者：
Hultgren, SJ
中科院分区：
文献类型：
--
作者：
Martinez, JJ;Mulvey, MA;Hultgren, SJ
大多数尿路致病性大肠杆菌（UPEC）菌株编码丝状粘附细胞器，称为1型皮利。我们已经确定，1型菌毛粘附素，FimH，不仅介导细菌的粘附，但也侵入人膀胱上皮细胞。相反，由另一种菌毛粘附素PapG介导的粘附并不启动细菌内化。FimH介导的侵袭需要宿主局部肌动蛋白重组、磷脂酰肌醇3-激酶（PI 3-kinase）激活和宿主蛋白酪氨酸磷酸化，而不需要Src家族酪氨酸激酶的激活。粘着斑激酶（FAK）Tyr 397的磷酸化以及FAK与PI 3-kinase、α-actinin与黏着斑蛋白形成复合物与1型菌毛介导的细菌侵袭相关。阻止细菌入侵的抑制剂也阻止了这些复合物的形成。我们的研究结果表明，UPEC菌株不是严格的细胞外病原体，1型菌毛粘附素FimH可以直接触发宿主细胞信号转导级联反应，导致细菌内化。
Most strains of uropathogenic Escherichia coli (UPEC) encode filamentous adhesive organelles called type 1 pili. We have determined that the type 1 pilus adhesin, FimH, mediates not only bacterial adherence, but also invasion of human bladder epithelial cells. In contrast, adherence mediated by another pilus adhesin, PapG, did not initiate bacterial internalization. FimH-mediated invasion required localized host actin reorganization, phosphoinositide 3-kinase (PI 3-kinase) activation and host protein tyrosine phosphorylation, but not activation of Src-family tyrosine kinases, Phosphorylation of focal adhesin kinase (FAK) at Tyr397 and the formation of complexes between FAK and PI 3-kinase and between a-actinin and vinculin were found to correlate with type 1 pilus-mediated bacterial invasion. Inhibitors that prevented bacterial invasion also blocked the formation of these complexes. Our results demonstrate that UPEC strains are not strictly extracellular pathogens and that the type 1 pilus adhesin FimH can directly trigger host cell signaling cascades that lead to bacterial internalization.