Antifungal efficacy of octylgallate and 4-isopropyl-3-methylphenol for control of Aspergillus

Authors: KIM, JONG - Former ARS Employee; Hart-Cooper, William; Chan, Kathleen - Kathy; Cheng, Luisa; Orts, William; JOHNSON, KAJ - Method Products, Pbc

Submitted to: Microbiology Discovery
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/2016
Publication Date: 12/21/2016
Publication URL: http://handle.nal.usda.gov/10113/5678137
Citation: Kim, J.H., Hart-Cooper, W.M., Chan, K.L., Cheng, L.W., Orts, W.J., Johnson, K. 2016. Antifungal efficacy of octylgallate and 4-isopropyl-3-methylphenol for control of Aspergillus. Microbiology Discovery. 4:2.

Interpretive Summary: There are increasing demands for safe, sustainable preservatives, which present no significant human health or environmental side effects, and therefore, could avoid negative consumer perception. Many natural products are “generally regarded as safe (GRAS)” compounds, and are potential sources of antifungal agents, either in their intact structure or as lead compounds for more potent structural analogs. Antifungal efficacy of GRAS compounds and conventional preservatives was investigated against fungal pathogens. The selected compounds octylgallate and 4-isopropyl-3-methylphenol, alone or in combination, effectively prevented fungal growth, where 4-isopropyl-3-methylphenol could also overcome fungicide tolerance of Aspergillus mutants. Application of proper types of surfactants was crucial for achieving optimum antifungal activity of compounds, thus emphasizing the importance of compound-compound or surfactant specificity during antifungal application.

Technical Abstract: Control of fungi is problematic, since effective methods for intervening fungal infection or contamination, especially for those resistant to conventional antifungal agents, are often very limited. Generally regarded as safe (GRAS) chemicals, such as natural compounds or their structural analogs could be potential sources of sustainable antifungal agents. As a proof of concept, antifungal efficacy of twenty-one GRAS compounds plus six conventional preservatives was investigated against Aspergillus brasiliensis, one of the challenge microbes for preservative evaluation. In particular, efficacy of octylgallate (OG) and 4-isopropyl-3-methylphenol (4I3M) was investigated for synergism as well as for overcoming fludioxonil (phenylpyrrole fungicide) tolerance of Aspergillus mutants. Out of twenty-one GRAS compounds examined (Clinical Laboratory Standards Institute protocol), five compounds showed the highest antifungal activity, viz., octylgallate (OG) > benzaldehyde > nonylgallate > 2-hydroxy-4-methylbenzaldehyde > carvacrol (higher to lower activity), where OG and benzaldehyde exhibited fungicidality. For formulation purpose, synergism was further investigated between OG (showing the highest activity) and conventional preservatives. 4I3M was the most responsive preservative to OG, where antifungal efficacy of 4I3M was enhanced four-fold with OG + 4I3M combination. Yeast bioassay indicated 4I3M might negatively affect the ion and redox homeostasis in fungi. 4I3M further overcame fludioxonil tolerance of two oxidative signaling mutants of Aspergillus. Of note, while 4I3M and its natural derivatives (thymol, carvacrol) were compatible with two out of three surfactants tested, the remaining surfactant antagonized the activity of 4I3M and its derivatives. Therefore, comprehensive characterization of compound-compound or surfactant specificity/relationship is necessary when develop sustainable antifungals.