Population pathogenesis of tuberculosis

Project

Globally, tuberculosis causes some 1.5 million deaths every year. Nevertheless, there is great variability in the rates of infection of people exposed to Mycobacterium tuberculosis, and 90 per cent of those infected do not become ill. This is likely to be due, at least in part, to genetic variation between different strains of M. tuberculosis.

This programme will explore genetic variability in M. tuberculosis in a field site in Mexico. Samples of bacteria will be collected and classified according to their genetic characteristics. Strains showing particularly interesting clinical or epidemiological behaviour will be characterised further, to try to determine which genetic features might be responsible for such behaviours. To assess the biological significance of these features, the effects of genetically manipulated bacteria will be assessed in animal models. Finally, to determine the significance of the results for natural infections, the programme will search for associations between the strains identified and outbreaks of clinical disease.

Identification of the genes that make certain strains of M. tuberculosis particularly infectious would be a key step towards better diagnosis, more specific control strategies and improved vaccines - in Central America and potentially elsewhere too.

Applicants

Dr P M Small
Division of Infectious Disease and Geographic Medicine, Stanford University School of Medicine, Stanford University Medical Center, USA

Dr G K Schoolnik
Departments of Medicine and Medical Microbiology, Stanford University, USA

Professor D B Young
Department of Medical Microbiology, Imperial College School of Medicine at St Mary's, London, UK

Dr B D Robertson
Department of Medical Microbiology, Imperial College School of Medicine at St Mary's, London, UK

Dr M De L Garcia-Garcia
Institute Nacional de Salud Publica, Cuernavaca, Mexico

Dr J Sifuentes-Osornio
Laboratory De Microbiologia Clinica, Institute Nacional De Nutricion, Mexico City, Mexico