YihE kinase is a central regulator of programmed cell death in bacteria

Cell Rep. 2013 Feb 21;3(2):528-37. doi: 10.1016/j.celrep.2013.01.026. Epub 2013 Feb 14.


Stress-mediated programmed cell death (PCD) in bacteria has recently attracted attention, largely because it raises novel possibilities for controlling pathogens. How PCD in bacteria is regulated to avoid population extinction due to transient, moderate stress remains a central question. Here, we report that the YihE protein kinase is a key regulator that protects Escherichia coli from antimicrobial and environmental stressors by antagonizing the MazEF toxin-antitoxin module. YihE was linked to a reactive oxygen species (ROS) cascade, and a deficiency of yihE stimulated stress-induced PCD even after stress dissipated. YihE was partially regulated by the Cpx envelope stress-response system, which, along with MazF toxin and superoxide, has both protective and destructive roles that help bacteria make a live-or-die decision in response to stress. YihE probably acts early in the stress response to limit self-sustaining ROS production and PCD. Inhibition of YihE may provide a way of enhancing antimicrobial lethality and attenuating virulence.

Publication types

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

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Apoptosis* / drug effects
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • Endoribonucleases / metabolism
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Nalidixic Acid / pharmacology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Reactive Oxygen Species / metabolism


  • Anti-Infective Agents
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • MazE protein, E coli
  • MazF protein, E coli
  • Reactive Oxygen Species
  • CpxR protein, Bacteria
  • Nalidixic Acid
  • Protein-Serine-Threonine Kinases
  • YihE protein, E coli
  • Endoribonucleases