Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria

Cell Host Microbe. 2013 Mar 13;13(3):358-70. doi: 10.1016/j.chom.2013.02.004.


Thiol-group oxidation of active and allosteric cysteines is a widespread regulatory posttranslational protein modification. Pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus, use regulatory cysteine oxidation to respond to and overcome reactive oxygen species (ROS) encountered in the host environment. To obtain a proteome-wide view of oxidation-sensitive cysteines in these two pathogens, we employed a competitive activity-based protein profiling approach to globally quantify hydrogen peroxide (H2O2) reactivity with cysteines across bacterial proteomes. We identified ∼200 proteins containing H2O2-sensitive cysteines, including metabolic enzymes, transcription factors, and uncharacterized proteins. Additional biochemical and genetic studies identified an oxidation-responsive cysteine in the master quorum-sensing regulator LasR and redox-regulated activities for acetaldehyde dehydrogenase ExaC, arginine deiminase ArcA, and glyceraldehyde 3-phosphate dehydrogenase. Taken together, our data indicate that pathogenic bacteria exhibit a complex, multilayered response to ROS that includes the rapid adaption of metabolic pathways to oxidative-stress challenge.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Cysteine / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Hydrogen Peroxide
  • Mice
  • Mice, Inbred C57BL
  • Oxidation-Reduction
  • Oxidative Stress
  • Proteome / genetics
  • Proteome / metabolism*
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism*
  • Reactive Oxygen Species / metabolism
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism


  • Bacterial Proteins
  • Proteome
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Cysteine