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R419 Inhibitors of Pectobacterium Virulence Factors

Publication Date: 
22 August 2011
Author/Contact :
Author/Contact: 
Martin Welch

Contractor :
Contractor: 
University of Cambridge

Full Research Project Title: Low molecular weight inhibitors of (p)ppGpp-dependent virulence factor production by Erwinia carotovora subsp. atroseptica
Duration: July 2009 - March 2012

Aim: To utilise the understanding of the genes and pathways involved in soft rot to try and develop low molecular weight compounds that block some of the important steps that allow Pectobacterium atrosepticum to cause rotting.

Industry Challenge

Pectobacterium atrosepticum (Pba) (formerly known as Erwinia carotovora subsp. atroseptica (Eca)) is one of the main causative agents of tuber soft rot. It is also known as the cause of aerial stem rot (or “blackleg”). Although the economic cost of Pbarelated potato disease is difficult to accurately assess, given the size of the GB industry (5.9 million tons of potatoes were produced in 2008, with an average price of £125 per ton) these losses cumulatively run to millions of pounds annually. There are no effective anti-rot agents on the market. The development of such anti-rot interventions would therefore offer a significant benefit to the British potato industry.

Collaboration

University of Cambridge

Approach

The project builds on studies at the University of Cambridge which showed that production of the enzymes that lead to soft rot is controlled by the nutritional status of the Pba bacterium. 

The anticipated outcomes of this project are:

a)  Validation of ppGpp production/reception as a target for antibacterial compound development.  One or more small molecules which specifically block ppGpp-dependent production of plant cell wall-degrading enzymes in Eca.

b)  Definition of the ppGpp-controlled regulon in Eca, and the overlap of this with the rpoS and quorum sensing-controlled regulons.  The identity of secreted proteins (possible virulence determinants) associated with each regulon.
c)  Novel binding partners/adaptor proteins involved in SpoT/RelA-dependent sensing mechanisms, and new targets for ppGpp action.
 
Key Findings

The work has shown that colonies of Pba only produce plant cell wall degrading enzymes when they begin to run short of nutrients; and when they are present in sufficient numbers such that the production of enzymes is likely to result in disease. The process of causing disease in turn releases nutrients for the bacteria. The results have confirmed a particular signalling pathway, involved in the regulation of the production of the cell wall degrading enzymes, as a suitable target for the development of anti-rot agents. However, the identification of molecules that disrupt the pathway has not been possible within the lifetime of the project and will continue beyond the end of the project.

Reports and Key Words

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