title: Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria.
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 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.
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Eranthie
authors.initials: E
authors.lastname: Weerapana
authors.forename: Olesya
authors.initials: O
authors.lastname: Ulanovskaya
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Haihua
authors.initials: H
authors.lastname: Liang
authors.forename: Quanjiang
authors.initials: Q
authors.lastname: Ji
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.forename: Ye
authors.initials: Y
authors.lastname: Fu
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.forename: Chu
authors.initials: C
authors.lastname: Wang
authors.forename: Sophie
authors.initials: S
authors.lastname: Alvarez
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Hicks
authors.forename: Lefu
authors.initials: L
authors.lastname: Lan
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D003545:Cysteine / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D003545:Cysteine