EXACERBATION OF INVASIVE ASPERGILLOSIS BY THE IMMUNOSUPPRESSIVE FUNGAL METABOLITE, GLIOTOXIN

Invasive aspergillosis is a significant cause of death in immunocompro mised individuals. The majority of strains of the main causative agent , Aspergillus fumigatus, produce gliotoxin, a secondary metabolite wit h demonstrated in vitro immunosuppressive activity. Pretreatment of no rmally resistant mice with a single injection of a sublethal dose of g liotoxin was sufficient to make them susceptible to infection and subs equent death, after challenge with A. fumigatus spores. Animals infect ed with the non-gliotoxin producing strain survived significantly long er than those infected with a gliotoxin producer. We propose that the release of gliotoxin by A. fumigatus hyphae during infection can exace rbate the pathogenesis of aspergillosis.