title: Enhanced activity of strobilurin and fludioxonil by using berberine and phenolic compounds to target fungal antioxidative stress response.
abstract: OBJECTIVE
  Identify natural products that effectively target antioxidative signal transduction/stress response systems [i.e., mitogen-activated protein kinase (MAPK) pathway, mitochondrial superoxide dismutase (Mn-SOD)] of fungi. Enhance activity of strobilurin or fludioxonil with discovered compounds.
  
  
  RESULTS
  Enhancement of antifungal activity of strobilurins, inhibitors of complex III of the mitochondrial respiratory chain, was tested using berberine hemisulfate and different phenolic compounds. The Saccharomyces cerevisiae sod2Delta, a deletion mutant lacking Mn-SOD gene, was highly sensitive to berberine and veratraldehyde. Functional complementation analysis verified these compounds target Mn-SOD. Activity of strobilurin (25-50 micromol l(-1)) was elevated on most aspergilli and Penicillium expansum by co-application with berberine or veratraldehyde (2-4 mmol l(-1)). These compounds also prevented Aspergillus fumigatus MAPK mutants (sakADelta and mpkCDelta) from escaping toxicity of fludioxonil (a phenylpyrrole fungicide potentiated by the MAPK pathway), a typical phenotype of fungal MAPK mutants.
  
  
  CONCLUSIONS
  Strobilurin activity or prevention of fungal escape from fludioxonil toxicity can be enhanced by co-application of certain alkaloids or phenolics.
  
  
  CONCLUSIONS
  Natural products can be used to target cellular stress response systems in fungal pathogens and serve as alternatives/additives to commercial antifungal agents.
authors.affiliation: Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, Albany, CA 94710, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: B C
authors.initials: BC
authors.lastname: Campbell
authors.forename: N
authors.initials: N
authors.lastname: Mahoney
authors.forename: K L
authors.initials: KL
authors.lastname: Chan
authors.forename: R J
authors.initials: RJ
authors.lastname: Molyneux
authors.forename: G S
authors.initials: GS
authors.lastname: May
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001599:Berberine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004357:Drug Synergism; D005658:Fungi / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018869:Heat-Shock Response; D008689:Methacrylates / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010636:Phenols / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D000935:Antifungal Agents; D001599:Berberine; D004146:Dioxanes; D004149:Dioxoles; D008689:Methacrylates; D010636:Phenols; D011758:Pyrroles; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C108339:fludioxonil