Host-pathogen interactions in tuberculosis

Tuberculosis (TB) is one of the world’s major infectious diseases and continues to be a major public health challenge globally. Human tuberculosis (hTB) accounts for 2 million deaths annually, with around a third of the world’s population being infected with the pathogen Mycobacterium tuberculosis

There is both epidemiological and molecular data giving insights into why there are profound differences in the clinical presentation of tuberculosis. The central question focuses on whether distinct M. tuberculosis strains co-evolved with distinct human populations and if so, what are the molecular determinants of this association. We seek to determine whether there is a specific host-pathogen molecular dialogue between innate immunity and bacterial virulence factors.

The objectives of this proposal are to investigate the key initial interactions between host and pathogen in tuberculosis using genomic sequence data from host and pathogen. It is hypothesised that there is a specific host-pathogen dialogue involving the innate immune response to Mycobacterium tuberculosis infection which plays a central role in disease outcome. This specific response can be influenced by host susceptibility factors and pathogen determinants, playing a pivotal in disease progression.

Publications

1. Tsolaki A.G., Hirsh A. E., DeRiemer K., Enciso J.A., Wong M., Hannan M., Goguet Y. Aman K. Kato-Maeda M. and Small P.M. Functional and evolutionary genomics of Mycobacterium tuberculosis: Insights from genomic deletions in 100 strains. Proc Natl Acad Sci U S A. April 6, 2004; 101: 4865-4870.
2. Tsolaki A.G., Gagneux S., Pym A.S., Goguet Y., Kreiswirth B., and Van Soolingen D., and Small P.M.. Genomic Deletions classify the Beijing/W strains as a distinct genetic lineage of Mycobacterium tuberculosis: Implications for pathogenesis, epidemiology and evolution. Journal of Clinical Microbiology 2005 Jul;43(7):3185-91.
3. Hirsh A.E., Tsolaki A.G. DeRiemer, K., Feldman M. and Small P.M. Stable association between strains of Mycobacterium tuberculosis and their human host populations. Proc Natl Acad Sci U S A. April 6, 2004; 101: 4871-4876.