1. Methylxanthine Inhibit Fungal Chitinases and Exhibit Antifungal Activity
- Author
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Christopher Andrade, Kalliope Tsirilakis, Christy Kim, Alfin G. Vicencio, Arturo Casadevall, and David L. Goldman
- Subjects
Antifungal Agents ,Veterinary (miscellaneous) ,Cryptococcus ,Down-Regulation ,Applied Microbiology and Biotechnology ,Microbiology ,Article ,Aspergillus fumigatus ,Fungal Proteins ,Cell wall ,chemistry.chemical_compound ,Chitin ,Enzyme Inhibitors ,Cryptococcus neoformans ,Fungal protein ,biology ,Chitinases ,Fungi ,biology.organism_classification ,chemistry ,Biochemistry ,Xanthines ,Chitinase ,biology.protein ,Growth inhibition ,Agronomy and Crop Science - Abstract
Chitinases are necessary for fungal cell wall remodeling and cell replication. Methylxanthines have been shown to competitively inhibit family 18 chitinases in vitro. We sought to determine the effects of methylxanthines on fungal chitinases. Fungi demonstrated variable chitinase activity and incubation with methylxanthines (0.5–10 mM) resulted in a dose-dependent decrease in this activity. All fungi tested, except for Candida spp., demonstrated growth inhibition in the presence of methylxanthines at a concentration of 10 mM. India ink staining demonstrated impaired budding and decreased cell size for methylxanthine-treated Cryptococcus neoformans. C. neoformans and Aspergillus fumigatus treated with pentoxifylline also exhibited abnormal cell morphology. In addition, pentoxifylline-treated C. neoformans exhibited increased susceptibility to calcofluor and a leaky melanin phenotype consistent with defective cell wall function. Our data suggest that a variety of fungi express chitinases and that methylxanthines have antifungal properties related to their inhibition of fungal chitinases. Our results highlight the potential utility of targeting chitinases in the development of novel antifungal therapies.
- Published
- 2011