Fluconazole at subinhibitory concentrations induces the oxidative- and nitrosative-responsive genes TRR1, GRE2 and YHB1, and enhances the resistance of Candida albicans to phagocytes.
OBJECTIVE
To analyse the oxidative and nitrosative stress response in Candida albicans generated by fluconazole at subinhibitory concentrations, and the functional consequences of such a response for the interaction with phagocytic cells.


METHODS
The C. albicans CAI-4 strain carrying transcriptional fusions of the TRR1p, YHB1p and GRE2p genes to the Renilla reniformis luciferase LUC gene was pre-treated with subinhibitory concentrations of fluconazole and incubated with oxidants (diamide and hydrogen peroxide) or with the myelomonocytic cell line HL-60.


RESULTS
Fluconazole induced oxidative and nitrosative stress in a time- and dose-dependent manner as determined using oxidative- and nitrosative-specific gene reporters. At subinhibitory concentrations, fluconazole was able to induce protection in vitro to subsequent challenges with oxidants in both liquid and solid media, and also induced partial protection against the oxidative-mediated killing mechanisms of the myelocytic HL-60 cells.


CONCLUSIONS
Subinhibitory concentrations of fluconazole protect against oxidants and killing mediated by phagocytes.
Arana
David M
DM
Departamento de Microbiología II, Universidad Complutense de Madrid, Spain.
Nombela
César
C
Pla
Jesús
J
D000935:Antifungal Agents / Q000494:pharmacology*; D019677:Artificial Gene Fusion; D002176:Candida albicans / Q000187:drug effects* / Q000276:immunology*; D002460:Cell Line; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics / Q000378:metabolism; D050296:Microbial Viability; D015538:Nitrosation; D018384:Oxidative Stress; D010586:Phagocytes / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D013312:Stress, Physiological
D000935:Antifungal Agents; D005656:Fungal Proteins; D015725:Fluconazole; D049410:Luciferases, Renilla