TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Jiarui Zhou
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Xingmei Liu
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Chen Jin
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Le Liu
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Hongmin Sun
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Qian Wang
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Qiushi Wang
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Ruiying Liu
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Xiaoyu Zheng
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China
Yutao Liu
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China; Corresponding author
Yu Pang
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin 300457, P.R. China; Corresponding author
Summary: 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.
