Fusarium Fungal Toxin Screens Against Yeast Genome Deletion Collections to Define Novel Resistance Mechanisms

The plant pathogenic fungus Fusarium graminearum infects cereal crops worldwide causing significant yield and economic losses.  This disease is characterized by the deposition of the mycotoxin deoxynivalenol (DON) and related metabolites within the grain of infected crops (corn, wheat, barley, oats). Mycotoxins pose significant health risks for consumers of infected grains, and DON has been implicated in the pathogenicity of the fungus towards host cereal plants since Fusariumstrains unable to synthesize DON are less virulent than wild-type strains.

The homology between yeast and higher eukaryotic organisms means that high-throughput chemogenomic profiling in yeast has become a very powerful method to discover drug and toxin targets. DON is known to be a potent protein synthesis inhibitor of eukaryotic cells, however, other modes of action in plant cells are not well understood.  Our screening of the yeast heterozygous deletion collection on sub-lethal levels of DON has enabled us to identify some genes whose deletion in yeast led to increased resistance or increased sensitivity to DON.  This screen has identified several genes expected to be associated with DON tolerance and sensitivity such as those involved in protein synthesis, folding, transport, turnover, as well as some novel targets. These hits or suppressors of toxicity have been validated in sensitive yeast growth assays.  Our results lead us to believe that the method of yeast genome-wide screening of chemical toxins may prove useful in developing fungal pathogen resistant crops