Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection.
Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection.
复制标题
DOI：
10.1016/j.celrep.2022.110698
复制
发表时间：
2022-04
期刊：
影响因子：
8.8
通讯作者：
Yu Pang;Zhihui Cheng;Shenmin Zhang;Shujie Li;Xueping Li;Xiaodan Li;Xiao Zhang;Xiaoxiao Li;Yingxing Feng;Heting Cui;Zhen Chen;Lewen Liu;Qing Li;Jianxiao Huang;Mingqing Zhang;Siwei Zhu;Lei Wang;Lu Feng
中科院分区：
文献类型：
--
作者：
Yu Pang;Zhihui Cheng;Shenmin Zhang;Shujie Li;Xueping Li;Xiaodan Li;Xiao Zhang;Xiaoxiao Li;Yingxing Feng;Heting Cui;Zhen Chen;Lewen Liu;Qing Li;Jianxiao Huang;Mingqing Zhang;Siwei Zhu;Lei Wang;Lu Feng
尿路感染主要由尿路致病性大肠杆菌（UPEC）引起。 UPEC通过梭形囊泡感染膀胱上皮细胞（BEC），逃入胞浆以逃避胞吐作用，并建立细胞内细菌群落（IBC）以进行下一轮感染。 UPEC 囊泡逃逸机制仍不清楚。在这里，我们展示了 UPEC 感知宿主免疫反应并通过上调关键磷脂酶启动逃逸。 UPEC磷脂酶PldA破坏囊泡膜，并且囊泡中磷酸盐还原激活pldA表达。宿主磷酸盐转运蛋白 PIT1 位于梭形囊泡膜上，将磷酸盐转运到细胞质中。 UPEC 感染通过核因子 κB (NF-κB) 上调 PIT1，导致磷酸盐减少。沉默 PIT1 可阻止 BEC 中 UPEC 囊泡逃逸，抑制小鼠膀胱中 IBC 的形成，并保护小鼠免受 UPEC 感染。我们的研究结果揭示了病原菌对细胞内磷酸盐缺乏的反应和解决宿主防御的问题，并为开发治疗 UPEC 感染的新治疗药物提供了见解。
Urinary tract infections are predominantly caused by uropathogenicEscherichia coli(UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, andpldAexpression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulatesPIT1via nuclear factor κB (NF-κB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection.