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Front. Microbiol., 05 April 2012 | http://dx.doi.org/10.3389/fmicb.2012.00133

Dysregulation of ion homeostasis by antifungal agents

  • Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca2+ burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.

Keywords: Candida albicans, plant essential oils, terpenoid phenol, carvacrol, amiodarone, calcium burst, pH, vacuole

Citation: Zhang Y, Muend S and Rao R (2012) Dysregulation of ion homeostasis by antifungal agents. Front. Microbio. 3:133. doi: 10.3389/fmicb.2012.00133

Received: 15 February 2012; Paper pending published: 23 February 2012;
Accepted: 20 March 2012; Published online: 05 April 2012.

Edited by:

Bruce C. Campbell, Western Regional Research Centre, USA

Reviewed by:

Bruce C. Campbell, Western Regional Research Centre, USA
Jong H. Kim, United States Department of Agriculture-Agricultural Research Service, USA

Copyright: © 2012 Zhang, Muend and Rao. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: Rajini Rao, Department of Physiology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA. e-mail: rrao@jhmi.edu