Nutrient-dependent viability screen

The yeast Saccharomyces cerevisae is well known as a host for the expression of heterologous proteins. It is also exceptionally useful for nutrient-dependent viability screening, and is even more versatile than E. coli. Examples of the myriad ways in which genes encoding heterologous proteins can be functionally expressed in yeast for HTS are readily available [13,36-39], However, few applications for antiparasitic drug discovery have been described. 

Of interest is a recently described yeast-based, nutrient-dependent viability screen for inhibitors of protozoal dihydrofolate reductase (DHFR) [43,44], Antiprotozoal activity of DHFR inhibitors is well known, and DHFR- yeast complemented with the DHFR gene derived from the malaria parasite P. falciparum have been used to characterize the molecular pharmacology of resistance to the antimalarial DHFR inhibitors pyrimethamine and cycloguanil [45,46], The subsequent development of a screen was based on the demonstration that the protozoal... 

The availability of medicinal chemistry resources can decide which approach to take in the absence of chemistry, a specific enzyme inhibitor that does not distinguish between host and parasite has little value. If chemistry is available, however, identifying a specific enzyme inhibitor can lead to the discovery of parasite-selective compounds. Random screens that search for novel structures are based on the premise that discovery of a specific inhibitor is an extremely rare event, and so the nutrient-dependent viability format is more desirable for HTS. 

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