Journal Article

Biological consequences of petite mutations in <i>Candida glabrata</i>

Sophie Brun, Frédéric Dalle, Patrick Saulnier, Gilles Renier, Alain Bonnin, Dominique Chabasse and Jean-Philippe Bouchara

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 2, pages 307-314
Published in print August 2005 | ISSN: 0305-7453
Published online June 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki200
Biological consequences of petite mutations in Candida glabrata

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Objectives: To define the pathogenicity of respiration-deficient mutants of Candida glabrata, which present a reduced susceptibility to azoles, that are easily induced in vitro by exposure to these drugs or to ethidium bromide and that may be selected in vivo in patients receiving fluconazole.

Methods: Two wild-type isolates of C. glabrata were compared with their respective fluconazole- or ethidium bromide-induced petite mutants, regarding the carbohydrate and protein composition of the cell wall, as well as their surface physical properties, and also their adherence abilities and virulence in mice.

Results: Flow cytometric analysis of cell wall carbohydrates using several fluorescent lectins showed an increased binding of mutant cells to concanavalin A compared with their parent isolates, suggesting a greater availability or an increased amount of glucose–mannose residues at the cell surface in petite mutants. Likewise, some quantitative differences between parent and mutant isolates were shown by SDS–PAGE in protein extracts from blastoconidia. Regarding the surface physical properties, no significant differences were seen in the electrophoretic mobility determined by microelectrophoresis, but the two-phase partitioning method revealed a lower cell surface hydrophobicity for petite mutants. Moreover, mutant cells exhibited significant overexpression of CgEPA1 as revealed by real-time reverse transcription-PCR, but the adherence capacities to Caco-2 cells, a human enterocyte line, were not significantly different. Finally, in agreement with their slower growth, petite mutants were less virulent than parent isolates in a murine model of systemic infection.

Conclusion: This low virulence in mice suggests that petite mutants could be disregarded clinically although they may arise during fluconazole therapy.

Keywords: petite mutants; cell surface hydrophobicity; adherence; virulence

Journal Article.  5783 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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