Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection

Yu Pang; Zhihui Cheng; Si Zhang; Shujie Li; Xueping Li; Xiaodan Li; Xiao Zhang; Xiaoxiao Li; Yingxing Feng; Heting Cui; Zhen Chen; Le Liu; Qing Li; Jianxiao Huang; Mingqing Zhang; Siwei Zhu; Lei Wang; Lu Feng

doi:10.1016/j.celrep.2022.110698

Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection

Cell Rep. 2022 Apr 19;39(3):110698. doi: 10.1016/j.celrep.2022.110698.

Authors

Yu Pang¹, Zhihui Cheng², Si Zhang³, Shujie Li³, Xueping Li³, Xiaodan Li³, Xiao Zhang³, Xiaoxiao Li³, Yingxing Feng³, Heting Cui³, Zhen Chen³, Le Liu³, Qing Li³, Jianxiao Huang³, Mingqing Zhang⁴, Siwei Zhu⁴, Lei Wang⁵, Lu Feng⁶

Affiliations

¹ The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300121, China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
² The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
³ The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
⁴ The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300121, China.
⁵ The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300121, China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China. Electronic address: wanglei@nankai.edu.cn.
⁶ The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China. Electronic address: fenglu63@nankai.edu.cn.

PMID: 35443182
DOI: 10.1016/j.celrep.2022.110698

Abstract

Urinary tract infections are predominantly caused by uropathogenic Escherichia 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, and pldA expression 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 upregulates PIT1 via 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.

Keywords: CP: Immunology; bacterial escape from fusiform vesicles; host-pathogen interactions; urinary tract infection; uropathogenic Escherichia coli.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Epithelial Cells / metabolism
Escherichia coli Infections* / microbiology
Mice
Phosphate Transport Proteins / metabolism
Phosphates / metabolism
Phospholipases / metabolism
Urinary Bladder
Uropathogenic Escherichia coli* / metabolism

Substances

Phosphate Transport Proteins
Phosphates
Phospholipases