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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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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.
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.
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.
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