Fraction of total population that persisted after being subjected to antifungal drug fluphenazine

Range ~0.1 %
Organism Budding yeast Saccharomyces cerevisiae
Reference Gilad Yaakov, David Lerner, Kajetan Bentele, Joseph Steinberger and Naama Barkai, Coupling phenotypic persistence to DNA damage increases genetic diversity in severe stress, Nature Ecology & Evolution 1, Article number: 0016 (2017) doi:10.1038/s41559-016-0016 pdf link p.1 left column top paragraph & 3rd paragraph
Method Abstract: "[Investigators] report that spontaneous DNA damage triggers persistence in Saccharomyces cerevisiae by activating the general stress response, providing protection against a range of harsh stress and drug environments."
Comments P.1 left column top paragraph: "Phenotypic persisters are individual microbes that survive harsh treatments that kill the majority of their genetically identical sister cells (refs 1-11). Persistence has been described in many bacterial species, and was recently implicated in the ability of individual cancer cells to survive chemotherapy (refs 12,13). Revealing the stochastic event triggering persistence is a major challenge to eradicating this subpopulation. Drug persistence has not been described in budding yeast, but a small fraction of cells have been shown to survive harsh environmental stresses (refs 14-16). While survivors are always expected, [investigators] observed a clear signature of persistence when subjecting cells to the antifungal drug fluphenazine: following the initial rapid exponential decline in the fraction of living cells, death rate was significantly reduced, indicating a small subpopulation (~10^−3) of persisters (Fig. 1a)." P.1 left column 3rd paragraph: "[Investigators] examined whether high Hsp12 [Heat shock protein 12] expression predicts stress survival by sorting single cells expressing either high (top 0.1%, termed ‘extreme’) or normal (the remaining 99.9%, termed ‘control’) Hsp12-GFP (green fluorescent protein) into 96-well plates (Fig. 1c), and monitoring their ability to survive and generate a colony in a range of harsh stresses. In unstressed conditions, cells expressing extreme Hsp12 levels survived less well than control cells. In sharp contrast, extreme cells better survived practically all stress exposures (Fig. 1d,e). To verify that extreme cells maintain their advantage under competitive conditions, [they] co-sorted differentially labelled extreme and control cells into the same well at different initial frequencies, and measured the relative fraction of their progenies at saturation."
Entered by Uri M
ID 113260