Characterisation of the Burkholderia pseudomallei K96243 CPS I coding region.


Cuccui, J; Milne, TS; Harmer, N; George, AJ; Harding, SV; Dean, RE; Scott, AE; Sarkar-Tyson, M; Wren, BW; Titball, RW; Prior, JL; (2012) Characterisation of the Burkholderia pseudomallei K96243 CPS I coding region. Infection and immunity, 80 (3). pp. 1209-21. ISSN 0019-9567 DOI: 10.1128/IAI.05805-11

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Abstract

: Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions of Southeast Asia and Northern Australia. Both humans and a range of other animal species are susceptible to melioidosis, and the production of a group 3 polysaccharide capsule in B. pseudomallei is essential for virulence. B. pseudomallei capsular polysaccharide (CPS) I comprises unbranched manno-heptopyranose residues and is encoded by a 34.5-kb locus on chromosome 1. Despite the importance of this locus, the role of all of the genes within this region is unclear. We inactivated 18 of these genes and analyzed their phenotype using Western blotting and immunofluorescence staining. Furthermore, by combining this approach with bioinformatic analysis, we were able to develop a model for CPS I biosynthesis and export. We report that inactivating gmhA, wcbJ, and wcbN in B. pseudomallei K96243 retains the immunogenic integrity of the polysaccharide despite causing attenuation in the BALB/c murine infection model. Mice immunized with the B. pseudomallei K96243 mutants lacking a functional copy of either gmhA or wcbJ were afforded significant levels of protection against a wild-type B. pseudomallei K96243 challenge.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 22252864
Web of Science ID: 300621600034
URI: http://researchonline.lshtm.ac.uk/id/eprint/56629

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