MOLECULAR AND GENETIC APPROACHES TO SUPPRESSING FUNGAL PATHOGENS AND MYCOTOXIN CONTAMINATION
Location: Plant Mycotoxin Research
Title: Use of chemosensitization to overcome fludioxonil resistance in Penicillium expansum
Submitted to: Letters in Applied Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 13, 2010
Publication Date: June 30, 2010
Citation: Kim, J.H., Campbell, B.C., Mahoney, N.E., Chan, K.L., Molyneux, R.J., Xiao, C.L. 2010. Use of chemosensitization to overcome fludioxonil resistance in Penicillium expansum. Letters in Applied Microbiology. 51:177-183.
Interpretive Summary: One of the major problems facing modern day agriculture is parasitic fungi that attack crop plants. One chief fungal pathogen is Penicillium expansum, or blue mold. This mold is a major problem, causing spoilage of various fruit (e.g., apples, pears, oranges) during post-harvest storage. In addition to reducing the quality of the fruit for the fresh market, this fungus also produces a toxin called patulin, considered a food safety concern. Patulin is a known, natural carcinogen. As such, levels of this toxin are restricted for market-bound products. Thus, significant efforts are made using fungicides to control blue mold on post-harvest commodities. However, this mold has shown itself to be able to consistently develop resistance to these fungicides. We have found a way to overcome resistance in this fungus to two widely used commercial fungicides. We use safe, natural compounds to undermine the ability of the fungus to respond to stress. We call this "chemosensitization." Chemosensitization re-establishes fungicidal vulnerability in resistant fungi. Thus, chemosensitization appears to be a safe and economical means of addressing a quality and food safety issue of key concern in today's agriculture.
Penicillium expansum mutants (FR2 and FR3) resistant to fludioxonil, a phenylpyrrole fungicide, became susceptible through chemosensitization mediated by natural phenolics. Increased sensitivity of FR3 to oxidizing agents, compared to its parental strain (W2), indicated the oxidative stress response system of FR3, such as the mitogen-activated protein kinase (MAPK) pathway, became dysfunctional by UV-treatment. On the other hand, FR2 showed higher tolerance to oxidizing agents compared to its parental strain (W1), suggesting fludioxonil resistance of FR2 was based upon gain-of-function, possibly increased antioxidation activity, of this mutant. Fungal resistance to fludioxonil resulted from cell-linked interruption of normal redox homeostasis. Redox-active natural phenolics were identified as chemosensitizing agents. These agents suppressed fludioxonil resistance of FR2/FR3 when co-applied into the culture medium. Natural phenolics were also found that served as chemosensitizing agents for a conventional fungicide, strobilurin. The efficacy of using natural, safe products to serve as chemosensitizing agents for control of fungal pathogens is discussed.