Year: 2026
Type: preprint
Abstract: HlyF and CprA, virulence factors from Escherichia coli and Pseudomonas aeruginosa respectively, constitute a previously unrecognized family of cytoplasmic enzymes that drive virulence through the production of outer membrane vesicles (OMVs) enriched in toxic bioactive lipids. Here, we show that OMVs of bacteria producing HlyF/CprA impair host autophagic flux by targeting lysosomal function. Specifically, these OMV-associated lipids disrupt autophagosome–lysosome fusion and induce hallmark features of lysosomal dysfunctions, including defective acidification, cholesterol accumulation, and membrane permeabilization. These lipid-mediated alterations compromise lysosomal integrity and block autophagic degradation. Our findings reveal a novel mechanism by which bacterial lipids subvert lysosomal functions and host clearance pathways. Given the widespread expression of HlyF/CprA homologs across diverse pathogens, this work highlights lipid effectors as key determinants of pathogenesis.
Institutions: Inserm, École Nationale Vétérinaire de Toulouse, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Institut de Recherche en Santé Digestive, Université de Toulouse, Centre National de la Recherche Scientifique, Institut Toulousain des Maladies Infectieuses et Inflammatoires
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: Role of extracellular bacterial vesicles in the pathophysiology of hemolytic-uremic syndrome (HUS), G3104932707, Structure and function of the cellular target of the anti-Shiga toxin drug candidate Retro-2.1, G5296751580, G7080048889, France-BioImaging (Biological Imaging Next-Generation Instrument)
OpenAlex ID: W7214055933