Journal Article

Fluconazole at subinhibitory concentrations induces the oxidative- and nitrosative-responsive genes TRR1, GRE2 and YHB1, and enhances the resistance of Candida albicans to phagocytes

David M. Arana, César Nombela and Jesús Pla

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 65, issue 1, pages 54-62
Published in print January 2010 | ISSN: 0305-7453
Published online November 2009 | e-ISSN: 1460-2091 | DOI: https://dx.doi.org/10.1093/jac/dkp407
Fluconazole at subinhibitory concentrations induces the oxidative- and nitrosative-responsive genes TRR1, GRE2 and YHB1, and enhances the resistance of Candida albicans to phagocytes

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Objectives

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.

Keywords: C. albicans; adaptation; oxidative stress

Journal Article.  5803 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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