Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli
Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli
复制标题
DOI：
10.1111/j.1462-5822.2006.00691.x
复制
发表时间：
2006-04-01
影响因子：
3.4
通讯作者：
Mulvey, MA
中科院分区：
文献类型：
--
作者：
Eto, DS;Sundsbak, JL;Mulvey, MA
尿路致病性大肠杆菌（UPEC）菌株可以侵入终末分化的浅表膀胱上皮细胞并随后繁殖，形成大的生物膜样包涵体，称为荚膜。相比之下，在未成熟的膀胱细胞中，UPEC进入更安静的状态，并且经常不能明显地复制。由于未成熟的膀胱上皮细胞经历终末分化，肌动蛋白细胞骨架急剧减少，我们认为这一现象可能影响UPEC的细胞内命运。在这里，我们发现未分化膀胱细胞内的UPEC被运输到具有晚期内体和溶酶体关键特征的酸性室中。在基于细胞培养的研究中，这些含有upc的液泡经常被肌动蛋白丝网络所缠绕，肌动蛋白丝的破坏刺激了细胞内upc的生长和流出。在这个体外模型系统中，UPEC释放到宿主细胞质中进一步刺激细胞内细菌生长和豆荚样内含物的快速发育。这些包涵体，以及在体内小鼠模型中观察到的包涵体，与细胞角蛋白中间丝相关，可能作为细胞内生物膜形成的支架。我们的数据提示了复发性尿路感染的病因学基础，将膀胱细胞分化和伴随的肌动蛋白微丝的重新分配与膀胱上皮内静止的孔内储层的UPEC的复苏联系起来。
Strains of uropathogenic Escherichia coli (UPEC) can invade terminally differentiated superficial bladder epithelial cells and subsequently multiply, forming large biofilm-like inclusions referred to as pods. In contrast, within immature bladder cells UPEC enter a more quiescent state and often fail to replicate appreciably. As immature bladder epithelial cells undergo terminal differentiation the actin cytoskeleton is radically diminished, a phenomenon that we reasoned could influence the intracellular fate of UPEC. Here we show that UPEC within undifferentiated bladder cells is trafficked into acidic compartments having key features of late endosomes and lysosomes. These UPEC-containing vacuoles are often enmeshed within a network of actin filaments, the disruption of which stimulates intravacuolar growth and efflux of UPEC in cell culture-based studies. In this in vitro model system, release of UPEC into the host cytosol further stimulates intracellular bacterial growth and the rapid development of pod-like inclusions. These inclusions, as well as those observed using an in vivo mouse model, develop in association with cytokeratin intermediate filaments that may act as scaffolding for intracellular biofilm formation. Our data suggest an aetiological basis for recurrent urinary tract infections, linking bladder cell differentiation and the accompanying redistribution of actin microfilaments with the resurgence of UPEC from quiescent intravacuolar reservoirs within the bladder epithelium.