Regulated Stochasticity in a Bacterial Signaling Network Permits Tolerance to a Rapid Environmental Change

Cell. 2018 Mar 22;173(1):196-207.e14. doi: 10.1016/j.cell.2018.02.005. Epub 2018 Mar 1.


Microbial populations can maximize fitness in dynamic environments through bet hedging, a process wherein a subpopulation assumes a phenotype not optimally adapted to the present environment but well adapted to an environment likely to be encountered. Here, we show that oxygen induces fluctuating expression of the trimethylamine oxide (TMAO) respiratory system of Escherichia coli, diversifying the cell population and enabling a bet-hedging strategy that permits growth following oxygen loss. This regulation by oxygen affects the variance in gene expression but leaves the mean unchanged. We show that the oxygen-sensitive transcription factor IscR is the key regulator of variability. Oxygen causes IscR to repress expression of a TMAO-responsive signaling system, allowing stochastic effects to have a strong effect on the output of the system and resulting in heterogeneous expression of the TMAO reduction machinery. This work reveals a mechanism through which cells regulate molecular noise to enhance fitness.

Keywords: anaerobic respiration; bacterial fitness; bet hedging; fluorescent proteins; gene expression variability; oxygen; single-cell biology; trimethylamine oxide; two-component signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Anaerobiosis
  • Base Sequence
  • Binding Sites
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Methylamines / metabolism
  • Methylamines / pharmacology
  • Oxygen / metabolism
  • Periplasmic Proteins / chemistry
  • Periplasmic Proteins / genetics
  • Periplasmic Proteins / metabolism
  • Phosphotransferases / chemistry
  • Phosphotransferases / genetics
  • Phosphotransferases / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Signal Transduction*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Up-Regulation


  • Escherichia coli Proteins
  • IscR protein, E coli
  • Methylamines
  • Periplasmic Proteins
  • TorT protein, E coli
  • Transcription Factors
  • Phosphotransferases
  • TorS protein, E coli
  • trimethyloxamine
  • Oxygen