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Abstract
The aim of this study was to examine two benzo analogs, octylgallate (OG) and veratraldehyde (VT), as antifungal agents against strains of Aspergillus parasiticus and A.flavus (toxigenic or atoxigenic). Both toxigenic and atoxigenic strains used were capable of producing kojic acid, another cellular secondary product. A. fumigatus was used as a genetic model for this study. When applied independently, OG exhibits considerably higher antifungal activity compared to VT. The minimum inhibitory concentrations (MICs) of OG were 0.3–0.5 mM, while that of VT were 3.0–5.0 mM in agar plate-bioassays. OG or VT in concert with the fungicide kresoxim methyl (Kre-Me; strobilurin) greatly enhanced sensitivity of Aspergillus strains to Kre-Me. The combination with OG also overcame the tolerance of A. fumigatus mitogen-activated protein kinase (MAPK) mutants to Kre-Me. The degree of compound interaction resulting from chemosensitization of the fungi by OG was determined using checkerboard bioassays, where synergistic activity greatly lowered MICs or minimum fungicidal concentrations. However, the control chemosensitizer benzohydroxamic acid, an alternative oxidase inhibitor conventionally applied in concert with strobilurin, did not achieve synergism. The level of antifungal or chemosensitizing activity was also “compound—strain” specific, indicating differential susceptibility of tested strains to OG or VT, and/or heat stress. Besides targeting the antioxidant system, OG also negatively affected the cell wall-integrity pathway, as determined by the inhibition of Saccharomyces cerevisiae cell wall-integrity MAPK pathway mutants. We concluded that certain benzo analogs effectively inhibit fungal growth. They possess chemosensitizing capability to increase efficacy of Kre-Me and thus, could reduce effective dosages of strobilurins and alleviate negative side effects associated with current antifungal practices. OG also exhibits moderate antiaflatoxigenic activity.
Highlights
Controlling fungi that produce hepato-carcinogenic aflatoxins in crops, such as tree nuts, corn, peanuts, etc., is problematic as effective commercial fungicides for treating aflatoxigenic fungi are very limited (Roze et al, 2013)
We investigated the role of two benzo derivatives, octylgallate (OG) and veratraldehyde (VT), currently used as food additives, as antifungal agents against strains of A. flavus, A. parasiticus, or A. fumigatus
A. fumigatus sakA and mpkC mutants could serve as model strains for investigating potential modes of antifungal responses in congeners, such as A. flavus or A. parasiticus
Summary
Controlling fungi that produce hepato-carcinogenic aflatoxins in crops, such as tree nuts, corn, peanuts, etc., is problematic as effective commercial fungicides for treating aflatoxigenic fungi are very limited (Roze et al, 2013). Significant amounts of harvested crop can be made unsuitable for sale and consumption as a result of aflatoxin contamination. Very low level (parts per billion) of aflatoxin contamination can have a perniciously negative effect on food safety and economic value of a number of crops from year to year (Campbell et al, 2003). Effective methods are continually needed for control of aflatoxigenic fungal pathogens. Strobilurins were initially identified in the fungus Strobilurus tenacellus, and were synthetically developed into several subgroups, such as kresoxim methyl (Kre-Me), azoxystrobin, pyraclostrobin, etc. Strobilurins were initially identified in the fungus Strobilurus tenacellus, and were synthetically developed into several subgroups, such as kresoxim methyl (Kre-Me), azoxystrobin, pyraclostrobin, etc. (Bartlett et al, 2002 and references therein)
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