Award details

A novel glucan pathway for immune system evasion by pathogens and carbon management in differentiating bacteria

Reference	BBS/E/J/000CA443
Principal Investigator / Supervisor	Professor Stephen Bornemann
Co-Investigators / Co-Supervisors	Professor David Lawson
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	105,425
Status	Completed
Type	Institute Project
Start date	01/08/2011
End date	31/07/2014
Duration	36 months

Abstract

We have recently discovered a new metabolic pathway widespread in bacteria called the GlgE pathway. This pathway involves four enzymes that make a glucose polymer (glucan) that is utilised by different bacteria to suit their lifestyles. Mycobacterium tuberculosis is the causative agent of tuberculosis, which kills almost 2 million people each year. The GlgE pathway exists in this pathogenic bacterium and we have identified that blocking the defining enzyme of this pathway, GlgE, leads to death of the bacterial cells through a novel mechanism. Interestingly, the related bacterium Streptomyces coelicolor uses the GlgE pathway for a very different purpose. This is a soil-dwelling organism that has been extensively studied because it makes antibiotics and has a complex life cycle involving spore formation. The GlgE pathway appears to be involved in the management of carbon obtained from the environment, whereby carbon is mobilised and stored in the form of glucan at appropriate times through the bacterium’s lifecycle. We hypothesise that the GlgE glucan product has a specialised structure in order that it can be differentiated from classical cytosolic glycogen and be exported more easily to the outer surface of the mycobacterial cell. The GlgE glucan will be defined by the last two enzymes of the pathway; GlgE, which makes the linear polymer backbone, and GlgB, which introduces branches. We will use a combination of protein crystallography and site-directed mutagenesis to determine how these enzymes control the structure of the glucan. In addition, we will explore how these enzymes are regulated. Knowledge of how the GlgE pathway operates and is regulated is important in the development of novel therapies against tuberculosis.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Microbiology, Structural Biology
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

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