Mutants in the Candida glabrata glycerol channels are sensitized to cell wall stress

Sara E. Beese-Sims, Shih Jung Pan, Jongmin Lee, Elizabeth Hwang-Wong, Brendan P Cormack, David E. Levin

Research output: Contribution to journalArticle

Abstract

Many fungal species use glycerol as a compatible solute with which to maintain osmotic homeostasis in response to changes in external osmolarity. In Saccharomyces cerevisiae, intracellular glycerol concentrations are regulated largely by the high osmolarity glycerol (HOG) response pathway, both through induction of glycerol biosynthesis and control of its flux through the plasma membrane Fps1 glycerol channel. The channel activity of Fps1 is also controlled by a pair of positive regulators, Rgc1 and Rgc2. In this study, we demonstrate that Candida glabrata, a fungal pathogen that possesses two Fps1 orthologs and two Rgc1/-2 orthologs, accumulates glycerol in response to hyperosmotic stress. We present an initial characterization of mutants with deletions in the C. glabrata FPS1 (CAGL0C03267 [www.candidagenome.org) and FPS2 (CAGL0E03894) genes and find that a double mutant accumulates glycerol, experiences constitutive cell wall stress, and is hypersensitive to treatment by caspofungin, an antifungal agent that targets the cell wall. This mutant is cleared more efficiently in mouse infections than is wild-type C. glabrata by caspofungin treatment. Finally, we demonstrate that one of the C. glabrata RGC orthologs complements an S. cerevisiae rgc1 rgc2 null mutant, supporting the conclusion that this regulatory assembly is conserved between these species.

Original languageEnglish (US)
Pages (from-to)1512-1519
Number of pages8
JournalEukaryotic Cell
Volume11
Issue number12
DOIs
StatePublished - Dec 2012

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Candida glabrata
Glycerol
Cell Wall
caspofungin
Osmolar Concentration
Saccharomyces cerevisiae
Antifungal Agents
Homeostasis
Cell Membrane
Infection

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Beese-Sims, S. E., Pan, S. J., Lee, J., Hwang-Wong, E., Cormack, B. P., & Levin, D. E. (2012). Mutants in the Candida glabrata glycerol channels are sensitized to cell wall stress. Eukaryotic Cell, 11(12), 1512-1519. https://doi.org/10.1128/EC.00231-12

Mutants in the Candida glabrata glycerol channels are sensitized to cell wall stress. / Beese-Sims, Sara E.; Pan, Shih Jung; Lee, Jongmin; Hwang-Wong, Elizabeth; Cormack, Brendan P; Levin, David E.

In: Eukaryotic Cell, Vol. 11, No. 12, 12.2012, p. 1512-1519.

Research output: Contribution to journalArticle

Beese-Sims, SE, Pan, SJ, Lee, J, Hwang-Wong, E, Cormack, BP & Levin, DE 2012, 'Mutants in the Candida glabrata glycerol channels are sensitized to cell wall stress', Eukaryotic Cell, vol. 11, no. 12, pp. 1512-1519. https://doi.org/10.1128/EC.00231-12
Beese-Sims, Sara E. ; Pan, Shih Jung ; Lee, Jongmin ; Hwang-Wong, Elizabeth ; Cormack, Brendan P ; Levin, David E. / Mutants in the Candida glabrata glycerol channels are sensitized to cell wall stress. In: Eukaryotic Cell. 2012 ; Vol. 11, No. 12. pp. 1512-1519.
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