GSE184377
Aminoglycosides induce a bacterial senescent state that increases antibiotic tolerance in treatment-naïve cells
Antibiotics are a triumph of modern medicine, but their power to cure infections is being eroded through the evolution and dissemination of resistance.  Evolution of genetic resistance is in part facilitated by non-genetic resistance mechanisms that increase antibiotic tolerance buying time for evolutionary innovation.  Using live cell imaging, we discovered that Escherichia coli treated with aminoglycosides permanently lose the ability to divide within 4 hours, yet a majority of cells maintain membrane integrity and metabolic 2 days post treatment, and some continuing activity for up to > 4 days post treatment – a bacterial senescent-like state.  These cells, which we term zombies, exhibit dynamic gene expression and metabolomic profiles even after exiting the cell cycle.  Gene expression data revealed upregulated the phage shock protein response maintained membrane integrity.  Remarkably, these zombie cells, though unable to form new colonies, increase antibiotic tolerance of treatment-naïve cells, implying chemical communication.  Chemical supplementation and genetic knockouts showed that zombies communicate to treatment-naïve cells by secreting indole.  In summary, our study revealed a bacterial senescent-like state, induced by aminoglycosides, that modifies the antibiotic tolerance of multiple bacterial species.   Overall design: RNA-seq analysis of E. coli zombies during exposure to kanamycin (30ug/mL).  6 timepoints, 3 replicates/timepoint