TY - JOUR TI - A long-term epigenetic memory switch controls bacterial virulence bimodality AU - Ronin, Irine AU - Katsowich, Naama AU - Rosenshine, Ilan AU - Balaban, Nathalie Q A2 - Laub, Michael VL - 6 PY - 2017 DA - 2017/02/07 SP - e19599 C1 - eLife 2017;6:e19599 DO - 10.7554/eLife.19599 UR - https://doi.org/10.7554/eLife.19599 AB - When pathogens enter the host, sensing of environmental cues activates the expression of virulence genes. Opposite transition of pathogens from activating to non-activating conditions is poorly understood. Interestingly, variability in the expression of virulence genes upon infection enhances colonization. In order to systematically detect the role of phenotypic variability in enteropathogenic E. coli (EPEC), an important human pathogen, both in virulence activating and non-activating conditions, we employed the ScanLag methodology. The analysis revealed a bimodal growth rate. Mathematical modeling combined with experimental analysis showed that this bimodality is mediated by a hysteretic memory-switch that results in the stable co-existence of non-virulent and hyper-virulent subpopulations, even after many generations of growth in non-activating conditions. We identified the per operon as the key component of the hysteretic switch. This unique hysteretic memory switch may result in persistent infection and enhanced host-to-host spreading. KW - bimodal gene expression KW - non-genetic variability KW - hysteresis KW - virulence regulation KW - EPEC KW - PerABC JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -