April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Gliotoxin Mediates Fungal Survival During Aspergillus fumigatus Keratitis
Author Affiliations & Notes
  • S. M. Leal, Jr.
    Department of Pathology,
    Case Western Reserve University, Cleveland, Ohio
  • K. J. Kwon-Chung
    Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
  • E. Pearlman
    Department of Ophthalmology and Visual Sciences,
    Case Western Reserve University, Cleveland, Ohio
  • Footnotes
    Commercial Relationships  S.M. Leal, Jr., None; K.J. Kwon-Chung, None; E. Pearlman, None.
  • Footnotes
    Support  RPB TRN108083 (SML); NIH NRSA EY019841(SML); NIHEY018612 (EP) NIH P30EY011373 (EP)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 6338. doi:
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      S. M. Leal, Jr., K. J. Kwon-Chung, E. Pearlman; Gliotoxin Mediates Fungal Survival During Aspergillus fumigatus Keratitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6338.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Gliotoxin is a cytotoxic secondary metabolite produced by several Aspergillus species, which induces apoptosis in macrophages and inhibits NADPH oxidase-dependent reactive oxygen species (ROS) formation in neutrophils. As macrophages and neutrophils have an essential role in fungal killing during Aspergillus corneal infection, we examined the role of gliotoxin in a murine model of Aspergillus keratitis.

Methods: : Corneas of C57BL/6J mice were injected with A.fumigatus strain B-5233, or with the isogenic gliotoxin deficient strain delta gliP, or the reconstituted strain gliPR and clinical disease progression, neutrophil recruitment, fungal viability, cellular apoptosis, ROS synthesis, and gliotoxin production was assessed at 0, 24, 48, & 72 hr post-infection.

Results: : A.fumigatus

Conclusions: : Gliotoxin production by A.fumigatus during corneal infection enhances fungal survival by inhibiting ROS formation leading to increased corneal pathology and worse clinical disease outcome. Pharmacological antagonism of gliotoxin may be of potential therapeutic benefit in the treatment of patients with Aspergillus keratitis.

Keywords: fungal disease • cornea: basic science • microbial pathogenesis: experimental studies 

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