Comparison of school outbreaks of MTB

main research interests focus on host-pathogen interactions in tuberculosis and in particular I have been involved in investigating some recent outbreaks of tuberculosis in the UK (school outbreak in Leicester with Profs Mike Barer and Robert Wilkinson, Newton et al., PNAS 2006 103(42): 15594-8; school outbreak in Harrow with Robert Wilkinson, Anderson AJRCCM 2006 173(9):1038-42; outbreak in a Nepalese community living in London, unpublished) in which very high rates of infection occurred in tuberculosis patient contacts and /or unusually severe disease presented. These outbreaks have been well characterised clinically and phenotypically in vitro. All three were caused by distinct strains of MTB each with previously unreported genomic deletions (LSP) as determined through DNA microarray analysis and each appearing to subvert proinflammatory cytokine responses in vitro by macrophages. In collaboration with the University of Leicester we showed that one of the genomic LSP in the outbreak strain (Rv1519) was associated with an immune subverting phenotype. However I would now like to further investigate the cellular and molecular mechanisms by which the strains subvert the host immune response. To do this and as a starting point I think it would be ideal to sequence the genomes of the strains responsible for the outbreak in a school in Harrow and in the Nepalese community outbreak (the strain responsible for the school outbreak in Leicester has already been sequenced by Professor Mike Barer's group, Leicester and the Sanger Centre) and compare to reference strain H37Rv. This would in itself provide a wealth of clues to further study the genotypic-phenotypic relationships of these strains and specifically the mechanisms involved in subversion of the immune response.