ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin.Journal of cellular and molecular medicine · 2016Trial
- Beyond probiotics: Lacticaseibacillus rhamnosus as a multi-target antagonist of Pseudomonas aeruginosa infections.Folia microbiologica · 2026Review
- Article
- Microbial phenazines: biosynthesis, structural diversity, evolution, regulation, and biological significance.Microbiology and molecular biology reviews : MMBR · 2025Review
- Neutrophil death-more than meets the eye.Experimental hematology · 2025Review
- Taurine metabolism is modulated in Vibrio-infected Penaeus vannamei to shape shrimp antibacterial response and survival.Microbiome · 2022Article
- 2-Undecanone derived from Pseudomonas aeruginosa modulates the neutrophil activity.BMB reports · 2022Article
- Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence.PLoS pathogens · 2019Article
- Pseudomonas aeruginosa inhibits Rhizopus microsporus germination through sequestration of free environmental iron.Scientific reports · 2019Article
- Pyocyanin induces NK92 cell apoptosis via mitochondrial damage and elevated intracellular CaInnate immunity · 2019Article
- C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death.Protein & cell · 2018Article
- The Outcome of theJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Neutrophils and Bacterial Immune Evasion.Journal of innate immunity · 2018Review
- Multikingdom microscale models.PLoS pathogens · 2017Review
- IRF3 Inhibits Neutrophil Recruitment in Mice Infected with Pseudomonas aeruginosa.Inflammation · 2017Article
- A Formidable Foe Is Sabotaging Your Results: What You Should Know about Biofilms and Wound Healing.Plastic and reconstructive surgery · 2017Article
- Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins.Cellular microbiology · 2017Article
- Pseudomonas expression of an oxygen sensing prolyl hydroxylase homologue regulates neutrophil host responsesWellcome open research · 2017Article
- Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis.Advances in biological regulation · 2017Review
- Transient Proteotoxicity of Bacterial Virulence Factor Pyocyanin in Renal Tubular Epithelial Cells Induces ER-Related Vacuolation and Can Be Efficiently Modulated by Iron Chelators.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Neutrophils undergo rapid constitutive apoptosis that is accelerated following bacterial ingestion as part of effective immunity, but is also accelerated by bacterial exotoxins as a mechanism of immune evasion. The paradigm of pathogen-driven neutrophil apoptosis is exemplified by the Pseudomonas aeruginosa toxic metabolite, pyocyanin. We previously showed pyocyanin dramatically accelerates neutrophil apoptosis both in vitro and in vivo, impairs host defenses, and favors bacterial persistence. In this study, we investigated the mechanisms of pyocyanin-induced neutrophil apoptosis. Pyocyanin induced early lysosomal dysfunction, shown by altered lysosomal pH, within 15 min of exposure. Lysosomal disruption was followed by mitochondrial membrane permeabilization, caspase activation, and destabilization of Mcl-1. Pharmacological inhibitors of a lysosomal protease, cathepsin D (CTSD), abrogated pyocyanin-induced apoptosis, and translocation of CTSD to the cytosol followed pyocyanin treatment and lysosomal disruption. A stable analog of cAMP (dibutyryl cAMP) impeded the translocation of CTSD and prevented the destabilization of Mcl-1 by pyocyanin. Thus, pyocyanin activated a coordinated series of events dependent upon lysosomal dysfunction and protease release, the first description of a bacterial toxin using a lysosomal cell death pathway. This may be a pathological pathway of cell death to which neutrophils are particularly susceptible, and could be therapeutically targeted to limit neutrophil death and preserve host responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.