Award details

Nitrosative stress in enterobacteria - the S-nitrosoproteome and an assessment of cellular protective functions in vitro and in vivo

Reference	BB/E015247/1
Principal Investigator / Supervisor	Professor David O'Connor
Co-Investigators / Co-Supervisors
Institution	University of Southampton
Department	Centre for Biological Sciences
Funding type	Research
Value (£)	188,096
Status	Completed
Type	Research Grant
Start date	01/09/2007
End date	31/08/2010
Duration	36 months

Abstract

Nitric oxide (NO) is one of the most important small molecules in biology. NO is a key signalling molecule in plants and animals, a powerful weapon in the anti-microbial armoury of mammalian and plant cells, and is responsible in animals and plants for controlling numerous functions by targeting protein thiols, metal centres, and other biomolecules. In particular, the covalent attachment of NO groups to protein sulfhydryls and transition metals is a precisely regulated post-translational modification. Bacteria respond to NO by sensing NO and activating transcription of genes encoding protective enzymes, notably, in enterobacteria, Hmp (flavohaemoglobin) and NorVW (flavorubredoxin). However, the effectiveness of these defence systems in preventing or limiting cellular damage and the extent to which pathogens are damaged by NO in vivo are not understood. The purpose of this project is (a) identification of the protein and haem targets of the different nitrosative stress agents to which bacteria are exposed (including targets important in signalling, not only defence), and (b) an assessment of the effectiveness of the various NO detoxification and NO-responsive mechanisms in preventing this damage. The answers generated by this concerted transcriptomic, proteomic and biochemical study will provide new insights into a key bacterial process that is important in bacterial survival in natural environments as diverse as the phagolysosome of a macrophage, the gastrointestinal and urinary tracts, and soil and water where reactive nitrogen species exist. This proposal represents the first attempt to define the degree and specificity of protection afforded by Hmp, NorVW and other proteins that may be involved in the bacterial nitrosative stress response. Joint with BB/E015883/1

Summary

Please refer to the proposal submitted by the Lead Applicant: Professor Robert Poole, Molecular Biology & Biotechnology, University of Sheffield.

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/E015883/1 Nitrosative stress in enterobacteria - the S-nitrosoproteome and an assessment of cellular protective functions in vitro and in vivo

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