The resistance mechanism of B_P225F and B_H272R mutations in succinate dehydrogenase in Botrytis cinerea.

Botrytis cinerea populations resistant to succinate dehydrogenase inhibitors (SDHIs) represent a major problem for the sustainable development of modern agriculture. In the present study, the resistance mechanism of B_P225F and B_H272R mutations in B. cinerea SDH (BcSDH) resistant to SDHIs fungicides, including boscalid (BOS), penflufen (PEN), pydiflumetofen (PYD), fluopyram (FLU), and benzovindiflupyr (BEN), was uncovered. The biological assay results showed that both mutations exhibited different resistant factor (RF) for SDHIs. The molecular modeling results indicated that the B_P225F and B_H272R mutations had great effects on the conformational change of the binding pocket and the binding modes of inhibitors. For both mutations, the cation-π interaction between ligand and the residue of C_R88, playing an important contribution to the binding affinity in wild type (WT), was decreased in B_P225F and disappeared in B_H272R. It was interesting that an additional hydrogen bond (Hbond) established between inhibitors with B_R272 compensated for the reduction in binding energy that occurred with the B_H272R mutation. As a result, both mutant types (B_P225F and B_H272R) have a lower affinity when bound with SDHIs than the WT-BcSDH. The structural and mechanistic insights obtained from the present work will provide a valuable clue for designing novel SDH inhibitors to overcome drug resistance associated with B_P225F and B_H272R mutations.