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ABSTRACT: Purine auxotrophic starvation in budding yeast

We would like to present the abstract of keynote speaker Janis Liepins, who is a researcher in the institute of Microbiology and Biotechnology,  University of Latvia.

Purine auxotrophic starvation in budding yeast 

While virtually all nucleated mammalian cells are able to synthesize purine nucleotides de novo, most of protist and helminth parasites strictly depend on purine scavenging from their hosts. Thes metabolic pecularity, in turn, is an attractive targets for antiparasitic drugs [1]

Recently auxotrophic yeast strains have been used to model purine auxotrophic, parasitic protists [2]. Adenine auxotrophic S. cerevisiae has been used also to screen for protist Plasmodium falciparum (malaria) drugs. To effectively screen library of thousands candidates, robust high throughput (HT) yeast based assays are very helpful [3, 4].

To further exploit S. cerevisiae as tool to model parasitic eukaryotes and instrument for drug screening, details on mechanisms governing it’s phenotype formation during auxotrophic starvation should be clarified.

Yeast strain auxotrophy and lack of particular metabolite in the cultivation broth is example of synthetic starvation. Uracil and leucine starvation leads to lowered stress resistance and shortened half life [5, 6]. Adenine depletion, on the other hand, evokes stress (heat, weak acid and oxidative) resistant phenotype, improves desiccation tolerance and does not significantly affect cell half life. Adenine starved cell’s effectively arrest cell cycle in G1 and are insensitive to rapamycin treatment [7, 8]. Interestingly, purine starvation specific, uniform, phenotype has been observed for two strains (CEN.PK2 and W303), but not for BY4741 the latest is S. cerevisiae genetics standard parent strain (EUROSCARF deletion project). 

Yeast phenotypes evoked by purine depletion is not only side effects of cultivation in poorly defined medium, but can also serve as a model for several biological phenomena where purine metabolism is distorted. 

The results of this research will contribute to understanding of fundamental mechanisms how cell reacts to sudden synthetic starvation and if there are key elements that could be drugable to control eukaryotic parasites with similar metabolic features (auxotrophies). 

[1]     Carter NS, Rager N, & Ullman B 2003 Academic Press, London, UK: 197-223
[2]    Landfear SM, 2011. Eukaryotic cell, 10(4): 483-93.
[3]     Deniskin R, et al., 2016. Int. J. for Parasitol: Drugs and Drug Resistance 6(1): 1–11
[4]    Frame IJ, Deniskin R, Rinderspacher A, 2015. ACS Chem. Biol. 10(3): 775-83.
[5]    Boer VM, Amini S, Botstein D 2008. PNAS 105: 6930–35.
[6]     Klosinska MM, et. al., 2011. Genes Dev. 25(4): 336-49.
[7]     Kokina A, Kibilds J, Liepins J, 2014. FEMS Yeast Res. 14(5): 697-707.
[8]     Liepins J, 2015. PhD thesis, Rīga, University of Latvia