Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell Host Microbe. 2011 Jul 21;10(1):33-43. doi: 10.1016/j.chom.2011.06.004.

Multiple targets of nitric oxide in the tricarboxylic acid cycle of Salmonella enterica serovar typhimurium.

Author information

  • 1Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.

Abstract

Host nitric oxide (NO⋅) production is important for controlling intracellular bacterial pathogens, including Salmonella enterica serovar Typhimurium, but the underlying mechanisms are incompletely understood. S. Typhmurium 14028s is prototrophic for all amino acids but cannot synthesize methionine (M) or lysine (K) during nitrosative stress. Here, we show that NO⋅-induced MK auxotrophy results from reduced succinyl-CoA availability as a consequence of NO⋅ targeting of lipoamide-dependent lipoamide dehydrogenase (LpdA) activity. LpdA is an essential component of the pyruvate and α-ketoglutarate dehydrogenase complexes. Additional effects of NO⋅ on gene regulation prevent compensatory pathways of succinyl-CoA production. Microarray analysis indicates that over 50% of the transcriptional response of S. Typhimurium to nitrosative stress is attributable to LpdA inhibition. Bacterial methionine transport is essential for virulence in NO⋅-producing mice, demonstrating that NO⋅-induced MK auxotrophy occurs in vivo. These observations underscore the importance of metabolic targets for antimicrobial actions of NO⋅.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in

  • Another target for NO. [Cell Host Microbe. 2011]
PMID:
21767810
[PubMed - indexed for MEDLINE]
PMCID:
PMC3142370
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk