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JAC Advance Access originally published online on May 30, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):434-438; doi:10.1093/jac/dkl221
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Proteomic analysis of experimentally induced azole resistance in Candida glabrata

P. David Rogers1–,4,*, John-Paul Vermitsky5, Thomas D. Edlind5 and George M. Hilliard6

1 Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Center Memphis, TN 38163, USA 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center Memphis, TN 38163, USA 3 Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA 4 Children's Foundation Research Center at Le Bonheur Children's Medical Center Memphis, TN 38103, USA 5 Department of Microbiology and Immunology, Drexel University College of Medicine Philadelphia, PA 19129, USA 6 Department of Molecular Sciences, College of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA

Received 22 February 2006; returned 5 April 2006; revised 3 May 2006; accepted 5 May 2006

*Correspondence address. Children's Foundation Research Center of Memphis, Le Bonheur Children's Medical Center, 50 North Dunlap Street, Room 304 West Patient Tower, Memphis, TN 38103, USA. Tel: +1-901-572-5387; Fax: +1-901-448-1741; E-mail: drogers{at}utmem.edu

Objectives: The aim of the present study was to identify changes in the proteome of a laboratory-derived azole-resistant strain of Candida glabrata compared with its susceptible parent strain in an effort to identify proteins that are differentially expressed in association with azole resistance.

Methods: Soluble and membrane protein fractions were isolated from mutant strain F15 (fluconazole MIC > 128 mg/L) and parent strain 66032 (fluconazole MIC = 16 mg/L) grown to mid-log phase. Soluble proteins were resolved by both two-dimensional (2D) and one-dimensional (1D) polyacrylamide gel electrophoresis (GE) whereas membrane proteins were resolved by 1D GE. Spots or bands representing differentially expressed proteins were identified by matrix-assisted desorption ionization-time of flight mass spectroscopy (MALDI-TOF MS) and peptide mass fingerprinting.

Results: A total of 22 proteins were found to be more abundantly represented, and 3 proteins were found to be less abundantly represented, in strain F15 compared with strain 66032. These included up-regulation of the ATP-binding cassette transporter Cdr1p, the ergosterol biosynthesis enzyme Erg11p, proteins involved in glycolysis and glycerol metabolism, and proteins involved in the response to oxidative stress and cadmium exposure.

Conclusions: In addition to transcriptional regulation of Cdr1p, this study identified the differential expression of several proteins that may contribute to azole resistance and suggests the possibility for a post-transcriptional mechanism for increased expression of Erg11p.

Keywords: lanosterol demethylase , efflux pumps , antifungals


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