Growth Curves Reveal How Multicellularity Enhances Drug Resistance

Drug resistance is a major cause of failure in treating many infectious diseases. Today’s demands for accurate drug design and effective treatment strategies require precise drug response quantitation and modeling, coupled with fast experimental testing. In this work we chose the multicellular clump-forming budding yeast (Saccharomyces cerevisiae) Sigma 1278b, or TBR1 strain as the potential model of multicellular drug-resistant yeast. By deleting the AMN1 gene responsible for clumping, we obtained a unicellular strain with otherwise identical genetic background. Drug-specific responses of multicellular versus unicellular yeast revealed by quantitative growth curve analysis indicate that multicellularity promotes resistance, producing altered drug response profiles. Finally, detailed modeling of the growth curves suggests parameters associated with molecular processes underlying multicellular drug resistance in yeast and possibly other microbes.