Multisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance

• DOI: 10.1038/s41467-019-13127-z
• Publication Date: 2019-11-13T11:04:01Z
• Authors: Elizabeth A. Libby; Shlomi Reuveni; Jonathan Dworkin
• Keywords: Sasa; Multidrug tolerance; Histidine kinase

Abstract Isogenic populations of cells exhibit phenotypic variability that has specific physiological consequences. Individual bacteria within a population can differ in antibiotic tolerance, but whether this be regulated or is generally an unavoidable consequence stochastic fluctuations unclear. Here we report gene encoding bacterial (p)ppGpp synthetase Bacillus subtilis , sasA exhibits high levels extrinsic noise expression. We find by multisite phosphorylation the transcription factor WalR, mediated Ser/Thr kinase-phosphatase pair PrkC/PrpC, and Histidine kinase WalK two-component system. This regulatory intersection crucial for controlling appearance outliers; rare with unusually expression, having increased tolerance. create predictive model demonstrating probability given cell surviving treatment increases Therefore, used to strongly regulate