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Mycopathologia. 2011 Jan;171(1):11-21. doi: 10.1007/s11046-010-9342-1. Epub 2010 Jul 9.

Molecular mechanisms of resistance to 5-fluorocytosine in laboratory mutants of Candida glabrata.

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Groupe d'Etude des Interactions Hôte-Pathogène, UPRES-EA 3142, Université d'Angers, Bâtiment Montéclair, Centre Hospitalier Universitaire, 4 rue Larrey, 49933, Angers Cedex 9, France.


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.

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