Mechanism of resistance to the antibiotic trichothecin in the producing fungi.

Trichothecium roseum, an imperfecti fungus producer of the translation inhibitor trichothecin, is constitutively resistant to its product. Fusarium oxysporum, a fungi not described as a toxin producer, is sensitive to trichothecin but becomes resistant when grown in the presence of the drug. In both cases, the resistance occurs at the level of the ribosomes. In cell-free polypeptide polymerization systems, trichothecin resistance is associated with the presence of 60S subunits from the resistant organisms. Resistant ribosomes can be prepared in vitro by incubating sensitive ribosomes, from either non-induced F. oxysporum or Saccharomyces cerevisiae, with cell extracts from the resistant cells in the presence of S-adenosylmethionine. An in-vitro specific differential methylation is detected in the sensitive ribosomes but not in resistant particles using radioactive S-adenosylmethionine. The results indicate for the first time the existence in eukaryotic organisms of an antibiotic-resistance mechanism involving a ribosomal methylation similar to that described previously in prokaryotic systems.