Directed evolution predicts cytochrome b G37V target site modification as probable adaptive mechanism towards the QiI fungicide fenpicoxamid in Zymoseptoria tritici.

Acquired resistance is a threat to antifungal efficacy in medicine and agriculture. The diversity of possible resistance mechanisms and highly adaptive traits of pathogens make it difficult to predict evolutionary outcomes of treatments. We used directed evolution as an approach to assess the resistance risk to the new fungicide fenpicoxamid in the wheat pathogenic fungus Zymoseptoria tritici.

Artemisinin and its derivatives target mitochondrial c-type cytochromes in yeast and human cells.

Artemisinin and its derivatives kill malaria parasites and inhibit the proliferation of cancer cells. In both processes, heme was shown to play a key role in artemisinin bioactivation. We found that artemisinin and clinical artemisinin derivatives are able to compensate for a mutation in the yeast Bcs1 protein, a key chaperon involved in biogenesis of the mitochondrial respiratory complex III.

Chemicals or mutations that target mitochondrial translation can rescue the respiratory deficiency of yeast bcs1 mutants.

Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory deficiency.

Human Mitochondrial Cytochrome b Variants Studied in Yeast: Not All Are Silent Polymorphisms.

Variations in mitochondrial DNA (mtDNA) cytochrome b (mt-cyb) are frequently found within the healthy population, but also occur within a spectrum of mitochondrial and common diseases. mt-cyb encodes the core subunit (MT-CYB) of complex III, a central component of the oxidative phosphorylation system that drives cellular energy production and homeostasis. Despite significant efforts, most mt-cyb variations identified are not matched with corresponding biochemical data, so their functional and pathogenic consequences in humans remain elusive.

The antimalarial drug primaquine targets Fe-S cluster proteins and yeast respiratory growth.

Malaria is a major health burden in tropical and subtropical countries. The antimalarial drug primaquine is extremely useful for killing the transmissible gametocyte forms of Plasmodium falciparum and the hepatic quiescent forms of P. vivax.

Interplay between the hinge region of iron sulphur protein and the Qo site in the bc1 complex - Analysis of Plasmodium-like mutations in the yeast enzyme.

The respiratory chain bc1 complex is central to mitochondrial bioenergetics and the target of antiprotozoals. We characterized a modified yeast bc1 complex that more closely resemble Plasmodium falciparum enzyme. The mutant version was generated by replacing ten cytochrome b Qo site residues by P.

Fitness measurement reveals contrasting costs in homologous recombinant mutants of Botrytis cinerea resistant to succinate dehydrogenase inhibitors.

Botrytis cinerea is a pathogenic ascomycete fungus that causes gray mold on many crops. Chemical control remains the principal method for curbing this disease. However, fungicide efficacy may be compromised by the selection of resistant strains.

Site-directed mutagenesis of the P225, N230 and H272 residues of succinate dehydrogenase subunit B from Botrytis cinerea highlights different roles in enzyme activity and inhibitor binding.

Carboxamide fungicides target succinate dehydrogenase (SDH). Recent field monitoring studies have identified Botrytis cinerea isolates resistant to one or several SDH inhibitors (SDHIs) with amino acid substitutions in the SDH B subunit. We confirmed, by site-directed mutagenesis of the sdhB gene, that each of the mutations identified in field strains conferred resistance to boscalid in B.

Two promoter rearrangements in a drug efflux transporter gene are responsible for the appearance and spread of multidrug resistance phenotype MDR2 in Botrytis cinerea isolates in French and German vineyards.

In French and German vineyards, Botrytis cinerea isolates with multiple fungicide resistance phenotypes have been observed with increasing frequencies. Multidrug resistance (MDR) results from mutations that lead to constitutive overexpression of genes encoding drug efflux transporters. In MDR2 and MDR3 strains, overexpression of the major facilitator superfamily transporter gene mfsM2 has been found to result from a rearrangement in the mfsM2 promoter (type A), caused by insertion of a retroelement (RE)-derived sequence.