Berberine hydrochloride as a synergist to combat fungicide resistance in Botrytis cinerea

Overview

Botrytis cinerea, the fungal pathogen responsible for grey mold, poses a major threat to global crop production. Its increasing resistance to multiple fungicides, driven by efflux proteins that pump active ingredients out of fungal cells, undermines existing crop protection strategies. This research proposes berberine hydrochloride, a plant-derived alkaloid, as a synergist that inhibits these efflux transporters. By blocking the resistance mechanism, berberine hydrochloride restores the accumulation and effectiveness of co-applied fungicides, offering a practical approach to managing multidrug-resistant grey mold in the field.

Technical specifications

Key features:

• Targets ABC efflux transporters BcatrB, BcatrD, and BcatrK in Botrytis cinerea, which are responsible for multidrug resistance
• Demonstrated synergistic effects with five fungicides of distinct modes of action, including carbendazim (β-tubulin assembly), pyrimethanil (methionine biosynthesis), boscalid (SDHI), azoxystrobin (QoI), and difenoconazole (DMI)
• Molecular docking and homology modeling confirm that berberine hydrochloride binds to efflux protein active sites through π-π conjugation and hydrogen bonding, competitively blocking fungicide transport
• Improved fungicide accumulation in resistant fungal hyphae validated experimentally
• Natural compound origin with potential for integration into existing fungicide programs

Technology readiness level

Laboratory validation has confirmed synergistic fungicide activity and molecular binding interactions. Genetic transformation studies are planned to further validate the efflux inhibition mechanism through overexpression and knockout experiments in both wild-type and resistant strains, with completion expected within one year. The solution is at an early-to-mid stage of development, with proof-of-concept data established and further mechanistic validation underway. The research team is actively seeking partnerships for gene function expertise, biological genetics collaboration, and funding for key personnel to advance the project toward field application.