Respiration Inhibitors: Complex II

Abstract

The succinate dehydrogenase inhibitors (SDHIs) are a highly attractive group of fungicides with regard to their history of use, chemical innovations, and spectrum of targeted diseases. They are the most modern, broadly effective fungicide group available to farmers for their disease control programs. As the group name indicates, the mode of action of SDHIs is the inhibition of succinate dehydrogenase in the respiration chain. Along with the broadening of their disease control palette, the structural complexity of the SDHIs has been increased. Nevertheless, the currently known SDHIs share common chemical features necessary for fungicidal activity, suggesting a very similar binding to the target as demonstrated here by three-dimensional alignment and computational docking experiments. Different target site mutations have been found in laboratory mutants and field isolates of various fungal species. Modeling studies with different target site mutations indicated that some of the observed target alterations conferring resistance to SDHIs have a direct impact on the binding behavior of SDHIs, whereas other mutations influence SDHI binding by long-range structural rearrangement in the transmembrane region of complex II. A diverse picture is seen regarding the effects of these mutations on the sensitivity toward various SDHIs in various pathogens and thus regarding cross-resistance. Some mutations cause a loss of sensitivity to all currently commercialized SDHIs, but there are also mutations where no complete cross-resistance can be found. Therefore, it can be stated that cross-resistance between SDHIs exists in general, but phenotypically exceptions are observed.