Trichothecen-Resistance

Self-resistance to trichothecenes in fungi Trichothecene mycotoxins are inhibitors of eukaryotic protein biosynthesis – they are therefore toxic to humans and animals, to plants but also to fungi. Some species, e.g. Trichothecium roseum (grape dry rot pathogen) or Trichoderma species (e.g. T. brevicompactum) produce large amounts of highly fungitoxic compounds such as trichothecin and trichodermin, respectively. The goal of the project is to get insights into the molecular mechanisms allowing the toxin producing fungi to resist to their own toxin. Several hypotheses should be tested. One is that the ribosomes of the producers show target insensitivity due to amino-acid changes in the ribosomal protein L3 as described for mutants of Saccharomyces cerevisiae with increased toxin resistance. This will be tested by functional replacement of the yeast gene with the orthologs from resistant (and susceptible) filamentous fungi. Another hypothesis is that adaptive modifications dependent on S-adenosylmethionine occur by methylation of either ribosomal RNA or certain ribosomal proteins. The effect of two candidate methyltransferases should be tested. A further hypothesis is that the fungi can cope with toxin by being able chemically modify the toxin structure. An epoxide opening GST from F. graminearum that is able to protect transformed yeast against toxicity of trichothecin and trichodermin will be characterized.