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LATENT TUBERCULOSIS: New tools for the detection and clearance of dormant Mycobacterium tuberculosis

Objective

Although the definition of latency under a clinical point of view seems clear, the bacterial biology behind that clinical situation remains poorly understood. While dormant, the tubercle bacilli are considered to be under non-replicating (NR) stage. In such a condition, bacilli are not only difficult to be detected but also refractory to the standard treatments avoiding their clearance from the infected tissues. The proposal has been built with the intend of providing tools to understand the bacterial mechanisms that leads to metabolic stage of M. tuberculosis during dormancy as the basis of sorting out the detection and treatment of latent infection. Several models of analysis have been developed trying to characterize dormant tubercle bacilli. Those models are ranging from in vitro conditions, such as hypoxia or starvation, to in vivo analysis, such as the animal model. We propose not only to study a complete range of those previously tested conditions, but also checking some other putative newly described, such as the recently described adipocytes ex vivo model, the new developments of the classical model of hypoxia, and the use of guinea-pigs as more adequate animal model of latent infection. Moreover, a set of drug combinations will be applied to determine their capability of clearance of the bacterial load. Due to its central role in the bacterial metabolism and growth we will analyze the non-replicating stage of the M. tuberculosis bacilli by determining the pre-rRNA synthesis. Finally, the cellular and tissue distribution of dormant bacilli will be also tested during in vivo latent infection both in the animal model and in clinical human samples. Research on the metabolic conditions of the dormant bacilli inside hosts, will provide important and invaluable insight into the biology of M. tuberculosis. That knowledge may lead to the development of novel strategies targeted at the control of the latent infection.

Field of science

  • /natural sciences/biological sciences/microbiology/bacteriology
  • /medical and health sciences/clinical medicine/pneumology/tuberculosis

Call for proposal

FP7-HEALTH-2007-A
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

UNIVERSIDAD AUTONOMA DE MADRID
Address
Calle Einstein 3 Ciudad Univ Cantoblanco Rectorado
28049 Madrid
Spain
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 483 440
Administrative Contact
Ana Amigo (Ms.)

Participants (6)

ISTITUTO SUPERIORE DI SANITA
Italy
EU contribution
€ 468 299,50
Address
Viale Regina Elena 299
00161 Roma
Activity type
Research Organisations
Administrative Contact
Rosa Maria Martoccia (Dr.)
INSTITUT DE INVESTIGACIO EN CIENCIES DE LA SALUT GERMANS TRIAS I PUJOL
Spain
EU contribution
€ 310 160
Address
Ctra De Canyet S/n
08916 Badalona Barcelona
Activity type
Research Organisations
Administrative Contact
Cristina Vilaplana Massaguer (Dr.)
ST GEORGE'S HOSPITAL MEDICAL SCHOOL
United Kingdom
EU contribution
€ 389 384
Address
Cranmer Terrace
SW17 0RE London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Susan Mcpheat (Ms.)
INSTITUTO POLITECNICO NACIONAL
Mexico
EU contribution
€ 304 320
Address
Miguel Othon De Mendizabal Sn, Col. La Escalera
07320 Mexico Df
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Luis Antonio Jimenez-Zamudio (Dr.)
CORPORACION CORPOGEN
Colombia
EU contribution
€ 374 400
Address
Carrera 5 N° 66A-34
N/A Bogota
Activity type
Research Organisations
Administrative Contact
Luis Fernando Diaz (Mr.)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 386 000
Address
Rue Michel Ange 3
75794 Paris
Activity type
Research Organisations
Administrative Contact
Armelle Barelli (Ms.)