Autotransported proteins of Burkholderia pseudomallei. (360G-Wellcome-085972_Z_08_Z)

The autotransporters, a family of secreted or membrane anchored proteins from Gram-negative bacteria, are released from the bacteria through a pathway termed type V or autotransporter secretion. Many members of this family have been implicated as important or putative virulence factors in various bacterial pathogens. Each pathogen has an unique set of atotransported proteins, however there is a significant sequence conservation in some parts of such proteins among various species, so genes of pu tative autotransporters can be identified in the available genomic sequences. Following this, the autotransporter-encoding genes can be mutated, and phenotypes associated with such mutations could be assessed. The virulence-associated proteins could be identified and characterised. Such research will undoubtedly contribute to the understanding of molecular mechanisms underlying bacterial pathogenicity and may aid the discovery of new targets for antimicrobial and vaccine development. Here, we p ropose to analyse the repertoire and functions of the autotransported proteins from B. pseudomallei and to assess their role(s) in the bacterial-host cell interactions and virulence. Defined mutants in all autotransported-encoding genes will be created and analysed in vitro and in vivo. The biochemical functions of selected autotransporters will be investigated. This study will provide valuable insights into the B. pseudomallei virulence mechanisms.