S-nitroso proteome of Mycobacterium tuberculosis: Enzymes of intermediary metabolism and antioxidant defense.
The immune response to Mycobacterium tuberculosis (Mtb) includes expression of nitric oxide (NO) synthase (NOS)2, whose products can kill Mtb in vitro with a molar potency greater than that of many conventional antitubercular agents. However, the targets of reactive nitrogen intermediates (RNIs) in Mtb are unknown. One major action of RNIs is protein S-nitrosylation. Here, we describe, to our knowledge, the first proteomic analysis of S-nitrosylation in a whole organism after treating Mtb with bactericidal concentrations of RNIs. The 29 S-nitroso proteins identified are all enzymes, mostly serving intermediary metabolism, lipid metabolism, and/or antioxidant defense. Many are essential or implicated in virulence, including defense against RNIs. For each of two target enzymes tested, lipoamide dehydrogenase and mycobacterial proteasome ATPase, S-nitrosylation caused enzyme inhibition. Moreover, endogenously biotinylated proteins were driven into mixed disulfide complexes. Targeting of metabolic enzymes and antioxidant defenses by means of protein S-nitrosylation and mixed disulfide bonding may contribute to the antimycobacterial actions of RNIs.
Rhee
Kyu Y
KY
Division of International Medicine and Infectious Diseases, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Nathan
Carl F
CF
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020543:Proteome; D026361:Reactive Nitrogen Species / Q000378:metabolism*
D000975:Antioxidants; D001426:Bacterial Proteins; D020543:Proteome; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide