Zap1 control of cell-cell signaling in candida albicans biofilms

Shantanu Ganguly, Andrew C. Bishop, Wenjie Xu, Suman Ghosh, Kenneth W. Nickerson, Frederick Lanni, Jana Patton-Vogt, Aaron P. Mitchell

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Biofilms of Candida albicans include both yeast cells and hyphae. Prior studies indicated that a zap1Δ/Δ mutant, defective in zinc regulator Zap1, has increased accumulation of yeast cells in biofilms. This altered yeast-hypha balance may arise from internal regulatory alterations or from an effect on the production of diffusible quorum-sensing (QS) molecules. Here, we develop biosensor reporter strains that express yeastspecific YWP1-RFP or hypha-specific HWP1-RFP, along with a constitutive TDH3-GFP normalization standard. Seeding these biosensor strains into biofilms allows a biological activity assay of the surrounding biofilm milieu. A zap1Δ/Δ biofilm induces the yeast-specific YWP1-RFP reporter in a wild-type biosensor strain, as determined by both quantitative reverse transcription-PCR (qRT-PCR) gene expression measurements and confocal microscopy. Remediation of the zap1Δ/Δ zinc uptake defect through zinc transporter gene ZRT2 overexpression reverses induction of the yeast-specific YWP1-RFP reporter. Gas chromatography-mass spectrometry (GC-MS) measurements of known organic QS molecules show that the zap1Δ/Δ mutant accumulates significantly less farnesol than wild-type or complemented strains and that ZRT2 overexpression does not affect farnesol accumulation. Farnesol is a well-characterized inhibitor of hypha formation; hence, a reduction in farnesol levels in zap1Δ/Δ biofilms is unexpected. Our findings argue that a Zap1- and zinc-dependent signal affects the yeast-hypha balance and that it is operative in the low-farnesol environment of the zap1Δ/Δ biofilm. In addition, our results indicate that Zap1 is a positive regulator of farnesol accumulation.

Original languageEnglish (US)
Pages (from-to)1448-1454
Number of pages7
JournalEukaryotic Cell
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2011

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Ganguly, S., Bishop, A. C., Xu, W., Ghosh, S., Nickerson, K. W., Lanni, F., Patton-Vogt, J., & Mitchell, A. P. (2011). Zap1 control of cell-cell signaling in candida albicans biofilms. Eukaryotic Cell, 10(11), 1448-1454. https://doi.org/10.1128/EC.05196-11