ArticleNature communications2021
The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Comparison ofInfection and immunity · 2026Article
- Topical formulation of repurposed FDA-approved compounds inhibits Pseudomonas aeruginosa ExoU and improves corneal infection outcomes.PLoS pathogens · 2026Article
- Mechanism of Gzma-mediated GEF-H1 activation in intestinal epithelial cells leading to intestinal barrier dysfunction in sepsis.Clinical and translational medicine · 2026Article
- Comparison ofbioRxiv : the preprint server for biology · 2026Article
- Patatin-domain-containing (phospho)lipases under control: Mammalian co-regulators and pathogenic activation mechanisms.FEBS open bio · 2026Review
- Heat shock proteins at the crossroads of endosomal trafficking pathways.Cell biology and toxicology · 2025Review
- Interplay between T3SS effectors, ExoY activation, and cGMP signaling in Pseudomonas aeruginosa infection.Nature communications · 2025Article
- Pseudomonas fragi or not? Beyond MALDI-TOF in the frontier of Pseudomonas diversity.Medical microbiology and immunology · 2025Article
- RetS-mediated environmental sensing coordinates TetR-dependent regulation of type III secretion system and virulence inApplied and environmental microbiology · 2025Article
- Mucous Permeable Nanoparticle for Inducing Cuproptosis-Like Death In Broad-Spectrum Bacteria for Nebulized Treatment of Acute Pneumonia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Does Every Strain ofPathogens (Basel, Switzerland) · 2024Article
- Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus.Communications biology · 2024Article
- Proximity labelling reveals effects of disease-causing mutation on the DNAJC5/cysteine string protein α interactome.The Biochemical journal · 2024Article
- Article
- Review
- Cell lipid biology in infections: an overview.Frontiers in cellular and infection microbiology · 2023Review
- N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system.Science advances · 2022Article
- The Role ofToxins · 2021Review
- Host phospholipid peroxidation fuels ExoU-dependent cell necrosis and supports Pseudomonas aeruginosa-driven pathology.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pseudomonas aeruginosa can cause nosocomial infections, especially in ventilated or cystic fibrosis patients. Highly pathogenic isolates express the phospholipase ExoU, an effector of the type III secretion system that acts on plasma membrane lipids, causing membrane rupture and host cell necrosis. Here, we use a genome-wide screen to discover that ExoU requires DNAJC5, a host chaperone, for its necrotic activity. DNAJC5 is known to participate in an unconventional secretory pathway for misfolded proteins involving anterograde vesicular trafficking. We show that DNAJC5-deficient human cells, or Drosophila flies knocked-down for the DNAJC5 orthologue, are largely resistant to ExoU-dependent virulence. ExoU colocalizes with DNAJC5-positive vesicles in the host cytoplasm. DNAJC5 mutations preventing vesicle trafficking (previously identified in adult neuronal ceroid lipofuscinosis, a human congenital disease) inhibit ExoU-dependent cell lysis. Our results suggest that, once injected into the host cytoplasm, ExoU docks to DNAJC5-positive secretory vesicles to reach the plasma membrane, where it can exert its phospholipase activity.
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