Uropathogenic Escherichia coli Subverts Host Autophagic Defenses by Stalling Preautophagosomal Structures to Escape Lysosome Exocytosis.
J Infect Dis
; 230(3): e548-e558, 2024 Sep 23.
Article
en En
| MEDLINE
| ID: mdl-38330453
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autofagia
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Infecciones Urinarias
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Células Epiteliales
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Infecciones por Escherichia coli
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Exocitosis
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Escherichia coli Uropatógena
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Lisosomas
Límite:
Humans
Idioma:
En
Revista:
J Infect Dis
Año:
2024
Tipo del documento:
Article