Uropathogenic Escherichia coli Subverts Host Autophagic Defenses by Stalling Preautophagosomal Structures to Escape Lysosome Exocytosis.

Autor:	Li X; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Jiang L; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Zhang S; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China.; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China., Zhou J; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Liu L; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Jin C; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Sun H; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Wang Q; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Liu Y; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China., Pang Y; Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, People's Republic of China.; The Key Laboratory of Molecular Microbiology and Technology, Tianjin Economic-Technological Development Area Institute of Biological Sciences and Biotechnology, Nankai University, Ministry of Education, Tianjin, People's Republic of China.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Sep 23; Vol. 230 (3), pp. e548-e558.
DOI:	10.1093/infdis/jiae063
Abstrakt:	Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles and escapes into the cytosol by disrupting fusiform vesicle membrane using outer membrane phospholipase PldA, and establishes biofilm-like intracellular bacterial communities (IBCs) for protection from host immune clearance. Cytosolic UPEC is captured by autophagy to form autophagosomes, then transported to lysosomes, triggering the spontaneous exocytosis of lysosomes. The mechanism by which UPEC evades autophagy to recognize and form IBCs remains unclear. Here, we demonstrate that by inhibiting autophagic flux, UPEC PldA reduces the lysosome exocytosis of BECs. By reducing intracellular phosphatidylinositol 3-phosphate levels, UPEC PldA increases the accumulation of NDP52 granules and decreases the targeting of NDP52 to autophagy, hence stalling preautophagosome structures. Thus, our results uncover a critical role for PldA to inhibit autophagic flux, favoring UPEC escapes from lysosome exocytosis, thereby contributing to acute urinary tract infection. Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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