Keywords: Latent Tuberculosis; Dormancy models; Treatment of latent Tuberculosis.
It is estimated that one-third of the human population is latently infected with Mycobacterium tuberculosis, constituting a major reservoir of that mycobacterium. The clinical definition of latency is clear, but the bacterial biology underlying this clinical situation remains poorly understood.
While dormant, the tubercle bacilli are considered to be in a non-replicating (NR) stage. In such a condition, bacilli are not only difficult to detect but also refractory to the standard treatments, avoiding their clearance from the infected tissues.
The main aim of this project is to analyse the basic activity of M. tuberculosis during dormancy, and the changes in that activity with drug treatment. The project is developing tools to improve the detection and treatment of latent infection.
Several analysis models will be studied to characterise the dormant tubercle bacilli. Those models range from in vitro conditions, such as hypoxia or starvation, to in vivo analysis, such as the animal model. The consortium is studying previously tested models along with others that are newly described, such as the recently described adipocytes ex vivo model, the new developments of the classical model of hypoxia, and the use of the new animal model of latent infection. A set of drug combinations will be applied to determine their capability of clearance of the bacterial load. Due to its central role in bacterial metabolism and growth, the project will analyse the non-replicating stage of the M. tuberculosis bacilli by determining the pre-rRNA synthesis. This knowledge may lead to the development of novel strategies targeted at the control of the latent infection.
The project hopes to obtain new insight into the mechanisms leading to the establishment of latent tuberculosis, and to develop new approaches to the treatment of latency by:
Combined, this knowledge may lead to the development of novel strategies for controlling latent infection.
The project is envisaged to be widely applicable to several aspects of TB, as well as to the following:
Maria Jesus Garcia
Universidad Autonoma de Madrid
|Official Address||Other Information|
|1||Lanfranco Fattorini||Istituto Superiore di Sanita
|2||Pere-Joan Cardona||Institut de Investigacio en Ciencies de la Salut 'Germans trias I Pujol'
|3||Anthony Coates||St George's Hospital Medical School, University of London
|5||Jorge Gonzalez-y-Merchand||Instituto Politecnico Nacional, Escuela Nacional de Ciencias Biologicas
|6||Patricia del Portillo||Corporacion CorpoGen
|7||Olivier Neyrolles||Centre National de la Recherche Scientifique