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Nucleoside-diphosphate kinase of uropathogenic Escherichia coli inhibits caspase-1-dependent pyroptosis facilitating urinary tract infection.

Authors :
Li, Xueping
Zhou, Jiarui
Liu, Xingmei
Jin, Chen
Liu, Le
Sun, Hongmin
Wang, Qian
Wang, Qiushi
Liu, Ruiying
Zheng, Xiaoyu
Liu, Yutao
Pang, Yu
Source :
Cell Reports; Apr2024, Vol. 43 Issue 4, pN.PAG-N.PAG, 1p
Publication Year :
2024

Abstract

Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI. [Display omitted] • UPEC NDK promotes urinary tract infection by preventing superficial BEC exfoliation • UPEC NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP • UPEC OxyR indirectly upregulates ihf , which in turn activates ndk in response to ROS Li et al. report that NDK contributes to UPEC intracellular bacterial community formation and urinary tract infection. Mechanistically, UPEC NDK inhibits caspase-1-dependent pyroptosis, thereby preventing superficial bladder epithelial cell (BEC) exfoliation. This finding provides insights into the development of therapeutic agents to treat UPEC infection. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
26391856
Volume :
43
Issue :
4
Database :
Complementary Index
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
176719735
Full Text :
https://doi.org/10.1016/j.celrep.2024.114051