Wren Lab, Burkholderia pseudomallei
The bacterium Burkholderia pseudomallei is a short gram negative rod capable of infecting both phagocytic (image 1) and non phagocytic cells and is the causative agent of meliodosis. This is a disease of both humans and animals and is emerging as a significant cause of morbidity and mortality in tropical and sub-tropical areas of the world.
At the London School of Hygiene and Tropical Medicine a number of investigators are currently involved in understanding the virulence determinants of this organism. The first stage of a signature-tagged mutagenesis project was completed and resulted in the identification of 39 attenuated mutants. Selected mutants are undergoing further investigation to understand their role during infection. We are currently focusing on the multinucleated giant cell formation capabilities of mutants (image 2) as well as the roles of individual genes within the capsular polysaccharide encoding region. In collaboration with Assistant Professor Sunee Korbsrisate's group at Mahidol University, we have carried out an investigation of the transcriptional response of B. pseudomallei to salt stress.
Other projects:
Application of bacterial N-linked glycosylation systems in order to develop a subunit vaccine against B. pseudomallei.
The use of next generation sequencing technologies to interrogate the B. pseudomallei genome under various stress conditions.
Principal investigator: Brendan Wren
Co-Investigators: Jon Cuccui, Madeleine Moule, Sam Willcocks, Jiali Lim
Funder: Defence Science and Technology Laboratories, DSO Singapore
Output from the project:
- Cuccui, J., Milne, T.S., Harmer, N., George, A.J., Harding, S.V., Dean, R.E., Scott, A.E., Sarkar-Tyson, M., Wren, B.W., Titball, R.W., Prior, J.L. (2012). Characterisation of the Burkholderia pseudomallei K96243 Capsular Polysaccharide I Coding Region. Infect Immun 80(3):1209-1221. Epub 2012 Jan 17
- Pumirat, P.; Cuccui, J.; Stabler, R.A.; Stevens, J.M.; Muangsombut, V.; Singsuksawat, E.; Stevens, M.P.; Wren, B.W.; Korbsrisate, S. Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system. BMC Microbiol. (2010) Jun 14;10:171
- Titball RW, Russell P, Cuccui J, Easton A, Haque A, Atkins T, Sarkar-Tyson M, Harley V, Wren B, Bancroft GJ. Burkholderia pseudomallei: animal models of infection. Trans R Soc Trop Med Hyg. 2008 Dec;102 Suppl 1:S111-6
- Cuccui, J., Easton, A., Chu, K.K., Bancroft, G.J., Oyston, P.C.F., Titball, R.W., and Wren, B.W. (2007) Development of signature-tagged mutagenesis in Burkholderia pseudomallei to identify genes important in survival and pathogenesis. Infect. Immun. 75: 1186-1195
Image 1:
Wild type B. pseudomallei infecting J774 macrophage.
Image 2:
Giemsa stained J774 cells infected with B. pseudomallei.
