Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs

We transcriptionally profiled thousands of C. albicans untreated and drug-treated cells at early and late timepoints by modifieying a single cell platform for fungal setting. Our DROP-seq set up was able to capture transcriptional signals in ~20K C. albicans . We were able to show cell-cell heterogeneity in seemingly isogenic populations of C. albicans untreated cells that coupled with cell cycle checkpoints. We also observed that individuals treating with different anti-fungals were partitioned into 20 subpopulations. The data shows a bifurcation into two major responses, term ?? and ?? responses, two days post-treatment. A transition from ?? response to ?? response was observed at day 3 which stay consistent to day 6. Bulk DNA sequencing does not show genomic abberation to be related to either ?? or ?? responses and the resistance does not change from day two to day six in diffusion disk assay. This can be an evidence of selection for cells that are able to mount an efficient tolerance response to anti-fungals early post treatment.Targeting ?? cells, or genes and pathways that support the ?? to ?? transition are interesting avenues to block drug tolerance. Overall design: Transcription profiling of C.albicans before and after drug treatment with single cell approches.