Cortactin recruitment by enterohemorrhagic Escherichia coli O157:H7 during infection in vitro and ex vivo.
Cortactin recruitment by enterohemorrhagic Escherichia coli O157:H7 during infection in vitro and ex vivo.
复制标题
肠出血性大肠杆菌 O157:H7 在体外和离体感染期间招募 Cortactin。
DOI：
10.1128/iai.00140-08
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发表时间：
2008
影响因子：
3.1
通讯作者：
Frankel,Gad
中科院分区：
文献类型：
--
作者：
Mousnier,Aurelie;Whale,AndrewD;Schuller,Stephanie;Leong,JohnM;Phillips,AlanD;Frankel,Gad
肠出血性大肠杆菌 (EHEC) O157:H7 是一种重要的人类病原体，可通过附着和消除 (A/E) 病变定植于肠道粘膜；体内和离体 A/E 损伤的形成取决于 III 型分泌系统 (T3SS) 效应子 Tir。 EHEC 感染培养细胞会诱导局部肌动蛋白聚合，这依赖于 Tir 和第二种 T3SS 效应蛋白 TccP（也称为 EspFU）。最近，cortactin 被证明可通过其 SH3 结构域结合 Tir 和 TccP 的 N 末端，并在体外 EHEC 触发的肌动蛋白聚合中发挥作用。在这项研究中，我们研究了体外培养的细胞和离体粘膜表面（使用人回肠末端器官培养物[IVOC]）感染过程中皮质蛋白向肠出血性大肠杆菌粘附部位的募集情况。我们已经证明 Cortactin 在体外被募集到 TccP 和 N-WASP 下游的 EHEC 粘附位点。删除 Tir 的整个 N 末端或用丙氨酸替换 N 末端聚脯氨酸区域不会消除肌动蛋白聚合或皮质蛋白募集。相比之下，IVOC 中 Cortactin 募集到 EHEC 粘附位点是独立于 TccP 的。这些结果表明，cortactin 在体外和离体中通过不同的机制被募集到 EHEC 粘附位点，并表明 cortactin 可能在 EHEC 感染粘膜表面的过程中发挥作用。
EnterohemorrhagicEscherichia coli(EHEC) O157:H7 is an important human pathogen that colonizes the gut mucosa via attaching and effacing (A/E) lesions; A/E lesion formation in vivo and ex vivo is dependent on the type III secretion system (T3SS) effector Tir. Infection of cultured cells by EHEC leads to induction of localized actin polymerization, which is dependent on Tir and a second T3SS effector protein, TccP, also known as EspFU. Recently, cortactin was shown to bind both the N terminus of Tir and TccP via its SH3 domain and to play a role in EHEC-triggered actin polymerization in vitro. In this study, we investigated the recruitment of cortactin to the site of EHEC adhesion during infection of in vitro-cultured cells and mucosal surfaces ex vivo (using human terminal ileal in vitro organ cultures [IVOC]). We have shown that cortactin is recruited to the site of EHEC adhesion in vitro downstream of TccP and N-WASP. Deletion of the entire N terminus of Tir or replacing the N-terminal polyproline region with alanines did not abrogate actin polymerization or cortactin recruitment. In contrast, recruitment of cortactin to the site of EHEC adhesion in IVOC is TccP independent. These results imply that cortactin is recruited to the site of EHEC adhesion in vitro and ex vivo by different mechanisms and suggest that cortactin might have a role during EHEC infection of mucosal surfaces.