ArticleExperimental eye research2007
Mutation of the phospholipase catalytic domain of the Pseudomonas aeruginosa cytotoxin ExoU abolishes colonization promoting activity and reduces corneal disease severity.
Article in Experimental eye research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Topical formulation of repurposed FDA-approved compounds inhibits Pseudomonas aeruginosa ExoU and improves corneal infection outcomes.PLoS pathogens · 2026Article
- ThemBio · 2025Article
- Contact Lens Wear Alters Transcriptional Responses to Pseudomonas aeruginosa in Both the Corneal Epithelium and the Bacteria.Investigative ophthalmology & visual science · 2025Article
- Contact Lens Wear Alters Transcriptional Responses tobioRxiv : the preprint server for biology · 2024Article
- Article
- Autophagy in the normal and diseased cornea.Experimental eye research · 2022Review
- An Organ System-Based Synopsis ofVirulence · 2021Review
- A pipeline to evaluate inhibitors of the Pseudomonas aeruginosa exotoxin U.The Biochemical journal · 2021Article
- Contact lens-related corneal infection: Intrinsic resistance and its compromise.Progress in retinal and eye research · 2020Review
- Review
- Genetic features of Pseudomonas aeruginosa isolates associated with eye infections referred to Farabi Hospital, Tehran, Iran.International ophthalmology · 2019Article
- A novel murine model for contact lens wear reveals clandestine IL-1R dependent corneal parainflammation and susceptibility to microbial keratitis upon inoculation with Pseudomonas aeruginosa.The ocular surface · 2019Article
- MEDI3902 Correlates of Protection against Severe Pseudomonas aeruginosa Pneumonia in a Rabbit Acute Pneumonia Model.Antimicrobial agents and chemotherapy · 2018Article
- A Mouse Model for Ocular Surface Staphylococcus aureus Infection.Current protocols in mouse biology · 2017Article
- Bacterial Sphingomyelinases and Phospholipases as Virulence Factors.Microbiology and molecular biology reviews : MMBR · 2016Review
- The importance of the Pseudomonas aeruginosa type III secretion system in epithelium traversal depends upon conditions of host susceptibility.Infection and immunity · 2015Article
- Host response and bacterial virulence factor expression in Pseudomonas aeruginosa and Streptococcus pneumoniae corneal ulcers.PloS one · 2013Article
- Innate immune regulation of Serratia marcescens-induced corneal inflammation and infection.Investigative ophthalmology & visual science · 2012Article
- ExoS and ExoT ADP ribosyltransferase activities mediate Pseudomonas aeruginosa keratitis by promoting neutrophil apoptosis and bacterial survival.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Traversal of multilayered corneal epithelia by cytotoxic Pseudomonas aeruginosa requires the phospholipase domain of exoU.Investigative ophthalmology & visual science · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that ExoU, a type III secreted cytotoxin of Pseudomonas aeruginosa, causes acute cytotoxicity towards corneal epithelial cells in vitro, and contributes to corneal disease pathology and ocular colonization in vivo. Subsequently, we reported that ExoU represses phagocyte infiltration of infected corneas in vivo. ExoU has patatin-like phospholipase activity that is required for cytotoxic activity in vitro (mammalian cell injury and death) and for disease in a murine model of pneumonia. We hypothesized that the phospholipase activity was required for ExoU-mediated corneal disease and ocular colonization. Using the murine scarification model, corneal disease pathology was examined after inoculation with approximately 10(6)cfu of a P. aeruginosa effector mutant (PA103DeltaexoUexoT::Tc) complemented with either exoU (pUCPexoU), phospholipase-inactive exoU (pUCPexoUD344A) or a plasmid control (pUCP18). Eyes were photographed and disease severity scored at 24 and 48h post-infection. Viable bacteria colonizing infected eyes were quantified at 6 and 48h. Complementation with exoU caused significantly more pathology (increased disease severity scores) and enabled bacteria to better colonize (by approximately 1000-fold) at 48h as compared to phospholipase-inactive exoU which did not differ from plasmid control. Surprisingly, exoU did not contribute to early (6h) colonization. In-vitro assays confirmed that the phospholipase domain of exoU was required for cytotoxicity towards human corneal epithelial cells. Taken together these data show that the phospholipase activity of the P. aeruginosa cytotoxin, ExoU, plays a role in the pathogenesis of corneal infection via mechanism(s) occurring after initial colonization of a susceptible cornea.
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Registered trials
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