Molecular mechanisms of resistance to 5-fluorocytosine in laboratory mutants of Candida glabrata.
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.
Vandeputte
Patrick
P
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. patrick.vandeputte@etud.univ-angers.fr
Pineau
Laurent
L
Larcher
Gérald
G
Noel
Thierry
T
Brèthes
Daniel
D
Chabasse
Dominique
D
Bouchara
Jean-Philippe
JP
D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects*; D043525:Cytosine Deaminase / Q000235:genetics; D004252:DNA Mutational Analysis; D025141:Drug Resistance, Fungal; D005437:Flucytosine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D020125:Mutation, Missense; D010430:Pentosyltransferases / Q000096:biosynthesis; D013940:Thymidylate Synthase / Q000096:biosynthesis
D000935:Antifungal Agents; D005437:Flucytosine; D013940:Thymidylate Synthase; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D043525:Cytosine Deaminase; D005472:Fluorouracil