Proteomic analysis of experimentally induced azole resistance in Candida glabrata

Phillip Rogers, John Paul Vermitsky, Thomas D. Edlind, George M. Hilliard

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)434-438
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number2
DOIs
StatePublished - Aug 1 2006

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Candida glabrata
Azoles
Proteomics
Proteins
Fluconazole
Membrane Proteins
Ergosterol
Peptide Mapping
ATP-Binding Cassette Transporters
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Glycolysis
Proteome
Cadmium
Glycerol
Electrophoresis
Polyacrylamide Gel Electrophoresis
Mass Spectrometry
Oxidative Stress
Up-Regulation
Gels

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Proteomic analysis of experimentally induced azole resistance in Candida glabrata. / Rogers, Phillip; Vermitsky, John Paul; Edlind, Thomas D.; Hilliard, George M.

In: Journal of Antimicrobial Chemotherapy, Vol. 58, No. 2, 01.08.2006, p. 434-438.

Research output: Contribution to journalArticle

Rogers, Phillip ; Vermitsky, John Paul ; Edlind, Thomas D. ; Hilliard, George M. / Proteomic analysis of experimentally induced azole resistance in Candida glabrata. In: Journal of Antimicrobial Chemotherapy. 2006 ; Vol. 58, No. 2. pp. 434-438.
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