Quorum sensing in pathogenic Burkholderias
Overview
Burkholderia pseudomallei is a prevalent environmental pathogen in tropical areas of the world, particularly in Southeast Asia and Northern Australia. In endemic areas it causes a severe human disease, melioidosis, posing a public health challenge. Melioidosis brings with it high mortality, diagnostic and therapeutic challenges, and the failure of long term efforts to develop an effective vaccine. B. pseudomallei exhibits extensive genome variability including functional prophage in islands of laterally transferred genes. These components of genome variability may contribute to the variability of disease phenotypes in infected patients.
We are in the process of developing novel vaccine strains and identifying new therapeutic targets based on the genes that direct the pathogenicity of Burkholderia mallei (Bm) and Burkholderia pseudomallei (Bp). This study is a genome scale analysis of the function and regulation of the complex quorum sensing systems of Bm and Bp and their relationship to virulence in mammalian hosts. It employs the traditional application of mutant construction including loss-of-function and inducible overexpression mutant constructs, phenotype screening, and also whole genome microarray expression profiling. Virulence related phenotypes will be explored via the use of human macrophages and small animal virulence testing. Host response to infection will be explored using microarray expression profiling of genes in the human genomes upon infection of human macrophages in culture.
Funding