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Mycopathologia

, Volume 171, Issue 1, pp 11–21 | Cite as

Molecular Mechanisms of Resistance to 5-Fluorocytosine in Laboratory Mutants of Candida glabrata

  • Patrick VandeputteEmail author
  • Laurent Pineau
  • Gérald Larcher
  • Thierry Noel
  • Daniel Brèthes
  • Dominique Chabasse
  • Jean-Philippe Bouchara
Article

Abstract

Resistance to 5-fluorocytosine (5-FC) has been poorly investigated in the yeast Candida glabrata. This study was conducted on laboratory mutants obtained by exposure of a wild-type isolate to 5-FC. Based on their susceptibility to 5-fluorouracil (5-FU), two of these mutants were selected for further analysis of the molecular mechanisms of 5-FC resistance. One mutant, resistant to both compounds, exhibited a missense mutation in the gene coding the cytosine deaminase and a decrease in the expression level of the gene coding the uridine monophosphate pyrophosphorylase. The other mutant that showed a reduced susceptibility to 5-FC and 5-FU exhibited an overexpression of the genes coding the thymidylate synthase and a cytosine permease, associated with a missense mutation in the last gene. Thus, beside mutations in the FUR1 gene which represent the most common cause of resistance to 5-FC, other mechanisms may also occur in C. glabrata.

Keywords

Candida glabrata 5-Fluorocytosine Resistance mechanisms FUR1, FCY1 and FCY2 genes 

Notes

Acknowledgments

P.V. was a recipient of a grant from Angers Loire Metropole. The authors want to thank the Institut de Parasitologie de l’Ouest, Rennes, France, for supporting in part the cost of this work.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Patrick Vandeputte
    • 1
    • 2
    Email author
  • Laurent Pineau
    • 1
    • 5
  • Gérald Larcher
    • 1
  • Thierry Noel
    • 3
  • Daniel Brèthes
    • 4
  • Dominique Chabasse
    • 1
    • 2
  • Jean-Philippe Bouchara
    • 1
    • 2
  1. 1.Groupe d’Etude des Interactions Hôte-Pathogène, UPRES-EA 3142Université d’AngersAngers Cedex 9France
  2. 2.Laboratoire de Parasitologie-MycologieAngersFrance
  3. 3.Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, CNRS, UMR-5234Université Victor Segalen Bordeaux IIBordeauxFrance
  4. 4.Institut de Biochimie et Génétique Cellulaires, CNRS, UMR-5095Université Victor Segalen Bordeaux IIBordeauxFrance
  5. 5.Cytokines: structure, signalisation et prolifération tumorale, INSERM U564Université d’AngersAngersFrance

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