Yeast missing either of the last two steps in threonine biosynthesis (Thr1p or Thr4p) have myriad deleterious phenotypes not typically associated with amino acid auxotrophy, such as sensitivity to salts, high and low temperatures, pH, and radiation. Joanne M. Kingsbury and John H. McCusker of Duke University Medical Center, Durham, N.C., show that these mutations also attenuate Saccharomyces cerevisiae and Candida albicans virulence, and the mutants die at unprecedentedly high rates in serum, due to the naturally low concentrations of threonine in serum. "Rather than any of the deleterious phenotypes actually being due to threonine auxotrophy per se, we demonstrate that they are in fact due to the threonine biosynthetic intermediate, homoserine, that accumulates in these mutants, and acts as a toxic threonine analog," says Kingsbury. "Since these threonine biosynthetic enzymes are absent from humans, our studies validate Thr1p and Thr4p as promising targets for antimicrobial drugs."

[J. M. Kingsbury and J. H. McCusker. 2010. Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1delta) mutants. Eukaryot. Cell 9:717-728; and J. M. Kingsbury and J.H. McCusker, 2010. Fungal homoserine kinase (thr1delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation. Eukaryot. Cell 9:729-737.]