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

Xin Deng, Eranthie Weerapana, Olesya Ulanovskaya, Fei Sun, Haihua Liang, Quanjiang Ji, Yan Ye, Ye Fu, Lu Zhou, Jiaxin Li, Haiyan Zhang, Chu Wang, Sophie Alvarez, Leslie M. Hicks, Lefu Lan, Min Wu, Benjamin F. Cravatt, Chuan He

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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 H2O 2-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.

Original languageEnglish (US)
Pages (from-to)358-370
Number of pages13
JournalCell Host and Microbe
Volume13
Issue number3
DOIs
StatePublished - Mar 13 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Deng, X., Weerapana, E., Ulanovskaya, O., Sun, F., Liang, H., Ji, Q., Ye, Y., Fu, Y., Zhou, L., Li, J., Zhang, H., Wang, C., Alvarez, S., Hicks, L. M., Lan, L., Wu, M., Cravatt, B. F., & He, C. (2013). Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria. Cell Host and Microbe, 13(3), 358-370. https://doi.org/10.1016/j.chom.2013.02.004