Mycobacterial Genetics

  HEADProf. GICQUEL Brigitte /
  MEMBERSDr Babon Aurélie / Badell-Ocando Edgar / Belalova Martina / Dasgupta Arunava
Dos Vultos SANTOS Tiago / ELVIRO MestrE Olga / Dr FILLON-Jackson Mary
Jang Jichan / Dr Martino Angelo / / Dr Neyrolles Olivier / Rakotosamimanana Niaina
Dr Sola Christophe / Dr Stadthagen GOMES Gustavo / Dr Tailleux Ludovic / Tanné Antoine / Dr Winter Nathalie

  Annual Report

Tuberculosis (TB) remains a major public health problem, causing about two million deaths each year. The currently used BCG vaccine is not entirely protective, and the efficacy of antibiotic treatments for TB may be reduced by the emergence of multidrug-resistant (MDR) strains of bacteria. M. tuberculosis genetic markers, virulence factors and host immune responses induced by M. tuberculosis and BCG are characterized to identify targets for new drugs and new vaccines. Host genetic markers associated with susceptibility to TB are identified as collaborative studies.

Host-pathogen interactions. M. tuberculosis parasitizes host phagocytes. DC-SIGN has been identified as the major M. tuberculosis receptor in human phagocytes. Several bacterial genes involved in virulence and intracellular parasitism have been identified with various genetic approaches. Their products are tested as new drug targets. A two-component regulator of several of these genes, PhoP/PhoR, has been identified, thus leading to the construction of a new vaccine candidate providing a higher degree of protection against TB than BCG in animal models.

M. tuberculosis DNA has been detected by PCR in the fat tissue surrounding various organs in individuals with latent infections. In vitro, M. tuberculosis survives within adipocytes in a non-replicating state insensitive to the major anti-mycobacterial drug, isoniazid. Our results suggest that this tissue may serve as a vast reservoir in which the tubercle bacillus persists for long periods of time and results in latent TB.

Early steps in BCG vaccination. Although BCG is widely used, the immune mechanisms resulting in the establishment of partial protection are poorly understood. Our results show that neutrophils are the principal BCG host cells, rapidly recruited in both the dermis and the lymph nodes upon BCG vaccination. Neutrophils that have captured bacilli in peripheral tissues transport them to the lymphoid organs. Thus, neutrophils, like DCs, seem to migrate to the lymphoid tissues via the afferent lymphatic system and can transport live micro-organisms.

Molecular epidemiology of TB.Genetic markers specific for highly transmissible M. tuberculosis strains responsible for outbreaks, and MDR outbreaks in particular, have been studied. Specific alleles of putative genes involved in DNA repair have been identified. These results suggest that antimutator genes may play a role in the evolution of several families of M. tuberculosis strains. We identified mutT- and ogt-specific alleles in M. tuberculosis strains of the W-Beijing genotype. One of the four mutT genes, mutT1, is an antimutator in M. tuberculosis and M. smegmatis.



Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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