JAC Advance Access originally published online on June 15, 2005
Journal of Antimicrobial Chemotherapy 2005 56(2):307-314; doi:10.1093/jac/dki200
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biological consequences of petite mutations in Candida glabrata
1 Groupe d'Etude des Interactions Hôte-Parasite, UPRES-EA 3142, Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire, 4 rue Larrey, 49033 Angers Cedex, France; 2 Laboratoire de Parasitologie-Mycologie, Hôpital du Bocage, 21079 Dijon Cedex, France; 3 INSERM U 646, 10 rue André Boquel, 49100 Angers, France; 4 Laboratoire d'Immunologie, Centre Hospitalier Universitaire, 4 rue Larrey, 49033 Angers Cedex, France
Received 18 February 2005; returned 2 April 2005; revised 28 April 2005; accepted 20 May 2005
* Corresponding author. Tel: +33-02-41-35-34-72; Fax: +33-02-41-35-36-16; E-mail: jean-philippe.bouchara{at}univ-angers.fr
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
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Posteraro, R. Martucci, M. La Sorda, B. Fiori, D. Sanglard, E. De Carolis, A. R. Florio, G. Fadda, and M. Sanguinetti Reliability of the Vitek 2 Yeast Susceptibility Test for Detection of In Vitro Resistance to Fluconazole and Voriconazole in Clinical Isolates of Candida albicans and Candida glabrata J. Clin. Microbiol., June 1, 2009; 47(6): 1927 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gulshan and W. S. Moye-Rowley Multidrug Resistance in Fungi Eukaryot. Cell, November 1, 2007; 6(11): 1933 - 1942. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cheng, C. J. Clancy, K. T. Nguyen, W. Clapp, and M. H. Nguyen A Candida albicans Petite Mutant Strain with Uncoupled Oxidative Phosphorylation Overexpresses MDR1 and Has Diminished Susceptibility to Fluconazole and Voriconazole Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1855 - 1858. [Abstract] [Full Text] [PDF]
|
|