Mitochondrial complex III Q i -site inhibitor resistance mutations found in laboratory selected mutants and field isolates.

BACKGROUND: Complex III inhibitors targeting the Qi -site have been known for decades; some are used or are being developed as anti-microbial compounds. Target site resistance mutations have been reported in laboratory-selected mutants and in field isolates. Here we present a brief over-view of mutations found in laboratory selected resistant mutants. We also provide a study of mutations observed in field isolates of Plasmopara viticola, in particular the ametoctradin resistance substitution, S34L that we analyzed in the yeast model.

RESULTS: The survey of laboratory mutants showed that resistance could be caused by a large number of substitutions in the Qi -site. Four residues seemed key in term of resistance, N31, G37, L198 and K228. Using yeast, we analyzed the effect of the ametoctradin resistance substitution S34L reported in field isolates of P.viticola. We showed that S34L caused a high level of resistance combined with a loss of complex III activity and growth competence.

CONCLUSION: The use of single site QiIs is expected to result in the selection of resistant mutants. However if the substitution is associated with a fitness penalty, as it could be the case with S34L, resistance development might not be an insuperable obstacle but careful monitoring is required. This article is protected by copyright. All rights reserved.