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The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

Author

Listed:
  • Jinglin L. Xie

    (University of Toronto)

  • Longguang Qin

    (University of Macau)

  • Zhengqiang Miao

    (University of Macau)

  • Ben T. Grys

    (University of Toronto
    University of Toronto)

  • Jacinto De La Cruz Diaz

    (University of Rochester)

  • Kenneth Ting

    (University of Toronto)

  • Jonathan R. Krieger

    (SPARC Biocentre)

  • Jiefei Tong

    (Peter Gilgan Centre for Research and Learning)

  • Kaeling Tan

    (University of Macau)

  • Michelle D. Leach

    (University of Toronto
    University of Aberdeen)

  • Troy Ketela

    (University of Toronto)

  • Michael F. Moran

    (University of Toronto
    SPARC Biocentre
    Peter Gilgan Centre for Research and Learning)

  • Damian J. Krysan

    (University of Rochester
    University of Rochester)

  • Charles Boone

    (University of Toronto
    University of Toronto)

  • Brenda J. Andrews

    (University of Toronto
    University of Toronto)

  • Anna Selmecki

    (Creighton University School of Medicine)

  • Koon Ho Wong

    (University of Macau)

  • Nicole Robbins

    (University of Toronto)

  • Leah E. Cowen

    (University of Toronto)

Abstract

The capacity to coordinate environmental sensing with initiation of cellular responses underpins microbial survival and is crucial for virulence and stress responses in microbial pathogens. Here we define circuitry that enables the fungal pathogen Candida albicans to couple cell cycle dynamics with responses to cell wall stress induced by echinocandins, a front-line class of antifungal drugs. We discover that the C. albicans transcription factor Cas5 is crucial for proper cell cycle dynamics and responses to echinocandins, which inhibit β-1,3-glucan synthesis. Cas5 has distinct transcriptional targets under basal and stress conditions, is activated by the phosphatase Glc7, and can regulate the expression of target genes in concert with the transcriptional regulators Swi4 and Swi6. Thus, we illuminate a mechanism of transcriptional control that couples cell wall integrity with cell cycle regulation, and uncover circuitry governing antifungal drug resistance.

Suggested Citation

  • Jinglin L. Xie & Longguang Qin & Zhengqiang Miao & Ben T. Grys & Jacinto De La Cruz Diaz & Kenneth Ting & Jonathan R. Krieger & Jiefei Tong & Kaeling Tan & Michelle D. Leach & Troy Ketela & Michael F., 2017. "The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00547-y
    DOI: 10.1038/s41467-017-00547-y
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