Crucial role of Ca2+ /CN signalling pathway in the antifungal activity of disenecioyl-cis-khellactone against Botrytis cinerea

Pest Manag Sci. 2022 Nov;78(11):4649-4659. doi: 10.1002/ps.7085. Epub 2022 Aug 17.

Abstract

Background: Botrytis cinerea causes grey mould and is one of the most destructive fungal pathogens affecting important fruit and vegetable crops. In preliminary studies, we found that disenecioyl-cis-khellactone (DK) had strong antifungal activity against several fungi species including B. cinerea [half maximal effective concentration (EC50 ) = 11.0 μg mL-1 ]. In this study, we aimed to further evaluate the antifungal activity of DK against B. cinerea and determine the role of calcium ion/calcineurin (Ca2+ /CN) signalling pathway on its antifungal effect.

Results: DK was effective against B. cinerea in both in vitro and in vivo assays. Exogenous Ca2+ reduced the antifungal activity of DK. The combination of DK and cyclosporine A (CsA) did not exhibit an additive effect against B. cinerea. In contrast to CsA, DK reduced the intracellular Ca2+ concentration in B. cinerea. DK bound to calcineurin A (cnA) and up-regulated the expression of PMC1 and PMR1 genes. Moreover, DK sensitivity of △bccnA significantly decreased compared with that of Bc05.10 strain.

Conclusion: DK is a promising lead compound for developing fungicides against B. cinerea. The Ca2+ /CN signalling pathway plays a crucial role in the DK antifungal activity, and cnA is one of the targets of DK against B. cinerea. DK directly reacts with cnA, which up-regulates the transcription of Ca2+ /CN-dependent target genes PMC1 and PMR1, decreasing the intracellular Ca2+ concentration and disturbing the intracellular Ca2+ balance, leading to cell death. © 2022 Society of Chemical Industry.

Keywords: Botrytis cinerea; Ca2+/CN signalling pathway; calcineurin A; disenecioyl-cis-khellactone.

MeSH terms

  • Antifungal Agents* / pharmacology
  • Botrytis
  • Calcineurin / pharmacology
  • Calcium / pharmacology
  • Coumarins
  • Cyclosporine / pharmacology
  • Fungicides, Industrial* / chemistry
  • Fungicides, Industrial* / pharmacology
  • Plant Diseases / microbiology

Substances

  • Antifungal Agents
  • Coumarins
  • Fungicides, Industrial
  • Cyclosporine
  • Calcineurin
  • Calcium
  • khellactone

Supplementary concepts

  • Botrytis cinerea