A long-term epigenetic memory switch controls bacterial virulence bimodality.
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 enteropathogenicE. 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 theperoperon as the key component of the hysteretic switch. This unique hysteretic memory switch may result in persistent infection and enhanced host-to-host spreading.
Racah Institute of Physics, Edmond J. Safra Campus, Faculty of Science, The Hebrew University of Jerusalem, Jerusalem, Israel.
Irine
I
Ronin
Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Naama
N
Katsowich
Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Ilan
I
Rosenshine
Racah Institute of Physics, Edmond J. Safra Campus, Faculty of Science, The Hebrew University of Jerusalem, Jerusalem, Israel.
Nathalie Q
0000-0001-8018-0766
NQ
Balaban
D044127:Epigenesis, Genetic; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development*; D008962:Models, Theoretical; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D037521:Virulence Factors
E. coli; EPEC; PerABC; bimodal gene expression; computational biology; hysteresis; infectious disease; microbiology; non-genetic variability; systems biology; virulence regulation