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Integrative physiology of Serratia secondary metabolism: proteomics virulence and functional genomics of pleiotropic twin antibiotic co-regulators

Reference	BB/C509090/1
Principal Investigator / Supervisor	Professor George Salmond
Co-Investigators / Co-Supervisors	Professor Kathryn Lilley
Institution	University of Cambridge
Department	Biochemistry
Funding type	Research
Value (£)	243,701
Status	Completed
Type	Research Grant
Start date	01/01/2005
End date	31/03/2008
Duration	39 months

Abstract

Strain ATCC39006 of Serratia is an enteric bacterium that is pathogenic in a Caenorhabditis elegans virulence assay, capable of rotting potato plants produces two secondary metabolite antibiotics (a carbapenem, 1-carbapen-2-em-3-carboxylic acid and a tripyrrole, red-pigment, prodigiosin) and makes pectinases and cellulases. We have identified a physiologically important group of core pleiotropic regulatory mutants that are co-ordinately affected in carbapenem and prodigiosin production. These key regulators include the quorum sensing (QS) regulators (SmalR) a novel putative DNA binding protein (PigP) and a central physiological regulator (Rap). The rap gene integrates information from both the QS and PigP regulators. We have identified a spectrum of additional regulatory genes that are targets for PigP or Rap in the overall regulatory hierarchy. We aim to test direct binding of the core regulator proteins (SmaR, PigP and Rap) to the 5 prime sequences of the subservient regulators in the hierarchy and define the relevant binding sites. We will use DiGE-based 2-D proteomics to identify novel proteins (and cognate genes) within the SmaR, PigP or Rap regulons to define the members of the overlapping regulons and identify new regulator-specific targets. The latter will be inactivated by marker exchange and their phenotypes assessed. The phenotypic assays will include the production of the secondary metabolites, production of the plant cell wall degrading enzymes, potato virulence, and virulence in a C. elegans bioassay. A search for potential super regulators of the key pigP gene will be conducted and possible and environmental and physiological signal inputs to pigP transcription will be investigated. The overall aim of this study is to understand the regulatory network involved in control of secondary metabolite production and determine new targets in plant and animal virulence for the core common regulator genes/proteins of this enterobacterial pathogen of animals, plants and insects.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Proteomics and Cell Function (PCF) [2003-2004]
Funding Scheme	X – not Funded via a specific Funding Scheme

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