Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

Annals of Clinical Microbiology and Antimicrobials

Research

Kathleen L Chan¹  Noreen Mahoney¹  Jong H Kim¹  Bruce C Campbell¹ 

[1] Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., 94710, Albany, CA, USA;

关键词: Minimum Inhibitory Concentration;    Antifungal Activity;    Thymol;    Mitochondrial Respiratory Chain;    Fractional Inhibitory Concentration Index;   

DOI  :  10.1186/1476-0711-10-23

 received in 2011-03-04, accepted in 2011-05-31,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundDisruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy.MethodsBenzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI).ResultsSeveral benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1 Δ, sod2 Δ, glr1 Δ) and two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus (sakA Δ, mpkC Δ), indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations. Effective inhibition of fungal growth can also be achieved using combinations of these benzaldehydes.ConclusionsNatural benzaldehydes targeting cellular antioxidation components of fungi, such as superoxide dismutases, glutathione reductase, etc., effectively inhibit fungal growth. They possess antifungal or chemosensitizing capacity to enhance efficacy of conventional antifungal agents. Chemosensitization can reduce costs, abate resistance, and alleviate negative side effects associated with current antifungal treatments.

【 授权许可】

Unknown   
© Kim et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.