Drug-dependent growth curve reshaping reveals mechanisms of antifungal resistance in Saccharomyces cerevisiae

Microbial drug resistance is an emerging global challenge. Current drug resistance assays tend to be simplistic, ignoring complexities of resistance manifestations and mechanisms, such as multicellularity. Here, we characterize multicellular and molecular sources of drug resistance upon deleting the AMN1 gene responsible for clumping multicellularity in a budding yeast strain, causing it to become unicellular. Computational analysis of growth curve changes upon drug treatment indicates that the unicellular strain is more sensitive to four common antifungals. Quantitative models uncover entwined multicellular and molecular processes underlying these differences in sensitivity and suggest AMN1 as an antifungal target in clumping pathogenic yeasts. Similar experimental and mathematical modeling pipelines could reveal multicellular and molecular drug resistance mechanisms, leading to more effective treatments against various microbial infections and possibly even cancers.

Automated summary

Microbial drug resistance is a global challenge, and current detection methods overlook the complexity of resistance mechanisms. Experimental and mathematical modeling can reveal the mechanisms of multicellular and molecular resistance, leading to more effective treatments for microbial infections and potentially even cancer.