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Methylxanthine Inhibit Fungal Chitinases and Exhibit Antifungal Activity

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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.

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Acknowledgments

We would like to thank Dr. Andre Nicola for his assistance with microscopy studies. Arturo Casadevall is supported by NIH grants AI033142, AI033774, AI052733, and HL059842.

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Author notes

  1. Kalliope Tsirilakis & Alfin G. Vicencio

    Present address: Department of Pediatrics, Steven and Alexander Cohen Children’s Medical Center of New York, New Hyde Park, NY, USA

Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital at Montefiore and Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA

    Kalliope Tsirilakis, Christy Kim, Alfin G. Vicencio, Christopher Andrade, Arturo Casadevall & David L. Goldman

  2. Division of Pediatric Pulmonology and Cystic Fibrosis Center, Cohen Children’s Medical Center of New York, New Hyde Park, NY, USA

    Kalliope Tsirilakis

  3. Divisions of Respiratory and Sleep Medicine, Children’s Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA

    Kalliope Tsirilakis & Alfin G. Vicencio

  4. Infectious Disease, Children’s Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA

    Christy Kim, Christopher Andrade & David L. Goldman

  5. Department of Microbiology and Immunology, Children’s Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA

    Arturo Casadevall & David L. Goldman

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  1. Kalliope Tsirilakis
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Correspondence to David L. Goldman.

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Tsirilakis, K., Kim, C., Vicencio, A.G. et al. Methylxanthine Inhibit Fungal Chitinases and Exhibit Antifungal Activity. Mycopathologia 173, 83–91 (2012). https://doi.org/10.1007/s11046-011-9483-x

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  • DOI: https://doi.org/10.1007/s11046-011-9483-x

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