Review ARTICLE

Front. Microbiol., 29 February 2012 | doi: 10.3389/fmicb.2012.00079

Chemosensitization as a means to augment commercial antifungal agents

  • Plant Mycotoxin Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, CA, USA

Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance.

Keywords: mycoses, azoles, natural products, antimycotic resistance, MAPK, cell wall/membrane integrity

Citation: Campbell BC, Chan KL and Kim JH (2012) Chemosensitization as a means to augment commercial antifungal agents. Front. Microbio. 3:79. doi: 10.3389/fmicb.2012.00079

Received: 17 December 2011; Accepted: 15 February 2012;
Published online: 29 February 2012.

Edited by:

Julianne Teresa Djordjevic, University of Sydney, Australia

Reviewed by:

Peter R. Williamson, National Institutes of Health, USA
Ameeta Agarwal, University of Mississippi, USA
Sharon Chen, Westmead Hospital, Australia

Copyright: © 2012 Campbell, Chan and Kim. 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: Bruce C. Campbell, Plant Mycotoxin Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, 800 Buchanan Street, Albany, CA 94710, USA. e-mail: bruce.campbell@ars.usda.gov

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