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Front. Microbiol. | doi: 10.3389/fmicb.2018.00502

Cyclic AMP pathway activation and extracellular zinc induce rapid intracellular zinc mobilization in Candida albicans

  • 1Department of Plant and Environmental Sciences, University of Copenhagen, Denmark
  • 2Pcovery, Denmark
  • 3Medical Research Council Centre for Medical Mycology, University of Aberdeen, United Kingdom

Zinc is an essential micronutrient, required for a range of zinc dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo 5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc- signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.

Keywords: cAMP, Zinc, Candida albicans, signaling, ER, ion homeostasis, bioimaging

Received: 27 Nov 2017; Accepted: 05 Mar 2018.

Edited by:

Dominique Sanglard, Universität von Lausanne, Switzerland

Reviewed by:

Malcolm Whiteway, Concordia University, Canada
Sascha Brunke, Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie, Hans Knöll Institut, Germany  

Copyright: © 2018 Kjellerup, Winther, Wilson and Fuglsang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Anja T. Fuglsang, University of Copenhagen, Department of Plant and Environmental Sciences, Thorvaldsensvej 40, Copenhagen, DK-1871 Frederiksberg, Denmark,