Mechanisms of persistence of B. pseudomallei. (360G-Wellcome-085162_A_08_Z)

£259,794

Melioidosis, caused by the Gram negative bacterium Burkholderia pseudomallei, is an often fatal disease of humans and animals. Human melioidosis is characterised by a profound difficulty in eradicating the pathogen either via the immune response or by antibiotics. Our hypothesis is that the ability of B. pseudomallei to establish a persistentinfection is central to the inefficiency of current antibiotic treatment, the susceptibility of individuals to re-infection and the difficulties associated with vaccine development. If the molecular basis of persistent infection was understood this would allow new pretreatments, therapies and diagnostics for melioidosis to be established and would address fundamental questions in the biology of persistent infection caused by bacteria. Our aims are to; i) Identify B. pseudomallei genes associated with chronic disease in humans and in mice ii) identify B. pseudomallei genes associated with the appearance of metabolically inactive (persister) cells in vitro which are resistant to antibiotics iii) construct bacterial mutants lacking genes identified in Aims 1&2 and assess their virulence and susceptibility to antibiotic treatment in a murine model of infection iv) investigate ways in which chronic or persistent infection might be more effectively controlled by antibiotics

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Grant Details

Amount Awarded 259794
Applicant Surname Titball
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2008-04-24T00:00:00+00:00
Financial Year 2007/08
Grant Programme: Title Project Grant
Internal ID 085162/A/08/Z
Lead Applicant Prof Richard Titball
Partnership Value 259794
Planned Dates: End Date 2012-11-30T00:00:00+00:00
Planned Dates: Start Date 2008-12-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South West