Changes in the proteome of Candida albicans in response to azole, polyene, and echinocandin antifungal agents

Christopher F. Hoehamer, Edwin D. Cummings, George M. Hilliard, Phillip Rogers

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The yeast Candida albicans is an opportunistic human fungal pathogen and the cause of superficial and systemic infections in immunocompromised patients. The classes of antifungal agents most commonly used to treat Candida infections are the azoles, polyenes, and echinocandins. In the present study, we identified changes in C. albicans protein abundance using two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectroscopy following exposure to representatives of the azole (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of antifungal agents. We identified 39 proteins whose abundance changed in response to ketoconazole exposure. Some of these proteins are involved in ergosterol biosynthesis and are associated with azole resistance. Exposure to amphotericin B altered the abundance of 43 proteins, including those associated with oxidative stress and osmotic tolerance. We identified 50 proteins whose abundance changed after exposure to caspofungin, including enzymes involved in cell wall biosynthesis and integrity, as well as the regulator of β-1,3-glucan synthase activity, Rho1p. Exposure to caspofungin also increased the abundance of the proteins involved in oxidative and osmotic stress. The common adaptive responses shared by all three antifungal agents included proteins involved in carbohydrate metabolism. Some of these antifungal-responsive proteins may represent potential targets for the development of novel therapeutics that could enhance the antifungal activities of these drugs.

Original languageEnglish (US)
Pages (from-to)1655-1664
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number5
DOIs
StatePublished - May 1 2010

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Echinocandins
Polyenes
Azoles
Antifungal Agents
Proteome
Candida albicans
caspofungin
Proteins
Ketoconazole
Amphotericin B
Oxidative Stress
Ergosterol
Osmotic Pressure
Electrophoresis, Gel, Two-Dimensional
Carbohydrate Metabolism
Immunocompromised Host
Infection
Candida
Cell Wall
Mass Spectrometry

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Changes in the proteome of Candida albicans in response to azole, polyene, and echinocandin antifungal agents. / Hoehamer, Christopher F.; Cummings, Edwin D.; Hilliard, George M.; Rogers, Phillip.

In: Antimicrobial Agents and Chemotherapy, Vol. 54, No. 5, 01.05.2010, p. 1655-1664.

Research output: Contribution to journalArticle

Hoehamer, Christopher F. ; Cummings, Edwin D. ; Hilliard, George M. ; Rogers, Phillip. / Changes in the proteome of Candida albicans in response to azole, polyene, and echinocandin antifungal agents. In: Antimicrobial Agents and Chemotherapy. 2010 ; Vol. 54, No. 5. pp. 1655-1664.
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