Mycopathologia

, Volume 173, Issue 2–3, pp 83–91 | Cite as

Methylxanthine Inhibit Fungal Chitinases and Exhibit Antifungal Activity

  • Kalliope Tsirilakis
  • Christy Kim
  • Alfin G. Vicencio
  • Christopher Andrade
  • Arturo Casadevall
  • David L. Goldman
Article

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.

Keywords

Chitinase Chitin Anti-fungal Methylxanthines Cryptococcus Aspergillus 

Notes

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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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Kalliope Tsirilakis
    • 1
    • 2
    • 3
    • 4
  • Christy Kim
    • 1
    • 5
  • Alfin G. Vicencio
    • 1
    • 2
    • 4
  • Christopher Andrade
    • 1
    • 5
  • Arturo Casadevall
    • 1
    • 6
  • David L. Goldman
    • 1
    • 5
    • 6
  1. 1.Department of PediatricsChildren’s Hospital at Montefiore and Albert Einstein College of MedicineBronxUSA
  2. 2.Department of PediatricsSteven and Alexander Cohen Children’s Medical Center of New YorkNew Hyde ParkUSA
  3. 3.Division of Pediatric Pulmonology and Cystic Fibrosis CenterCohen Children’s Medical Center of New YorkNew Hyde ParkUSA
  4. 4.Divisions of Respiratory and Sleep MedicineChildren’s Hospital at Montefiore and Albert Einstein College of MedicineBronxUSA
  5. 5.Infectious DiseaseChildren’s Hospital at Montefiore and Albert Einstein College of MedicineBronxUSA
  6. 6.Department of Microbiology and ImmunologyChildren’s Hospital at Montefiore and Albert Einstein College of MedicineBronxUSA

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