PMID:18070885

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Citation

Jarboe, LR, Hyduke, DR, Tran, LM, Chou, KJ and Liao, JC (2008) Determination of the Escherichia coli S-nitrosoglutathione response network using integrated biochemical and systems analysis. J. Biol. Chem. 283:5148-57

Abstract

During infection or denitrification, bacteria encounter reactive nitrogen species. Although the molecular targets of and defensive response against nitric oxide (NO) in Escherichia coli are well studied, the response elements specific to S-nitrosothiols are less clear. Previously, we employed an integrated systems biology approach to unravel the E. coli NO-response network. Here we use a similar approach to confirm that S-nitrosoglutathione (GSNO) primarily impacts the metabolic and regulatory programs of E. coli in minimal medium by reaction with homocysteine and cysteine and subsequent disruption of the methionine biosynthesis pathway. Targeting of homocysteine and cysteine results in altered regulatory activity of MetJ, MetR, and CysB, activation of the stringent response and growth inhibition. Deletion of metJ or supplementation with methionine strongly attenuated the effect of GSNO on growth and gene expression. Furthermore, GSNO inhibited the ArcAB two-component system. Consistent with the underlying nitrosative and thiol-oxidative chemistry, growth inhibition and the majority of the regulatory perturbations were dependent upon GSNO internalization by the Dpp dipeptide transporter. Contrastingly, perturbation of NsrR appeared to be a result of the submicromolar levels of NO released from GSNO and did not require GSNO internalization.

Links

PubMed Online version:10.1074/jbc.M706018200

Keywords

Amino Acids/genetics; Amino Acids/metabolism; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Biological Transport, Active/physiology; Dipeptides/genetics; Dipeptides/metabolism; Escherichia coli/genetics; Escherichia coli/growth & development; Escherichia coli/metabolism; Escherichia coli Infections/genetics; Escherichia coli Infections/metabolism; Gene Deletion; Nitric Oxide/metabolism; Oxidation-Reduction; Repressor Proteins/genetics; Repressor Proteins/metabolism; S-Nitrosoglutathione/metabolism; Trans-Activators/genetics; Trans-Activators/metabolism

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