Two cyclophilin A homologs with shared and distinct functions important for growth and virulence of Cryptococcus neoformans.

Published

Journal Article

Cyclophilin A is the target of the immunosuppressant cyclosporin A (CsA) and is encoded by a single unique gene conserved from yeast to humans. In the pathogenic fungus Cryptococcus neoformans, two homologous linked genes, CPA1 and CPA2, were found to encode two conserved cyclophilin A proteins. In contrast to Saccharomyces cerevisiae, in which cyclophilin A mutations confer CsA resistance but few other phenotypes, cyclophilin A mutations conferred dramatic phenotypes in C. neoformans. The Cpa1 and Cpa2 cyclophilin A proteins play a shared role in cell growth, mating, virulence and CsA toxicity. The Cpa1 and Cpa2 proteins also have divergent functions. cpa1 mutants are inviable at 39 degrees C and attenuated for virulence, whereas cpa2 mutants are viable at 39 degrees C and fully virulent. cpa1 cpa2 double mutants exhibited synthetic defects in growth and virulence. Cyclophilin A active site mutants restored growth of cpa1 cpa2 mutants at ambient but not at higher temperatures, suggesting that the prolyl isomerase activity of cyclophilin A has an in vivo function.

Full Text

Duke Authors

Cited Authors

  • Wang, P; Cardenas, ME; Cox, GM; Perfect, JR; Heitman, J

Published Date

  • June 2001

Published In

Volume / Issue

  • 2 / 6

Start / End Page

  • 511 - 518

PubMed ID

  • 11415984

Pubmed Central ID

  • 11415984

International Standard Serial Number (ISSN)

  • 1469-221X

Digital Object Identifier (DOI)

  • 10.1093/embo-reports/kve109

Language

  • eng

Conference Location

  • England