Unit: Mycobacterium Reference
Director: Véronique Vincent
A tuberculosis study in Cameroon showed a recent epidemiological change with a drastic decrease of Mycobacterium africanum, with less than 10% of cases. A new genetic family of M. tuberculosis recently emerged. This very homogenous family is highly prevalent, totalling more than 40% of cases.
New diagnostic techniques for tuberculosis are currently developed targeting manosylated proteins.
Mycobacterium National Reference Center (Gilles Marchal, Véronique Vincent, Cristina Gutiérrez-Perez, Anne Varnerot, Maria de Moura Goncalves, Nathalie Barilone, Cyril Dumontt)
Our laboratory is a National Reference Center and is implied in the surveillance of tuberculosis and other mycobacterial infections. The surveillance of multi-drug resistant tuberculosis, i.e. difficult to treat cases due to strains resistant to both major drugs isoniazide and rifampicin, is achieved by a systematic strain typing. Our laboratory is member of the WHO network of supranational laboratories for the surveillance of global antituberculous drug resistance. A training course for molecular typing techniques of tubercle bacilli has been organised since 2000. Member of the an ad hoc committee for the Conseil Supérieur d'Hygiène Publique de France, our CNR participated to recommendations of prevention and care of tuberculosis in France
Genetic biodiversity of tubercle bacilli in Cameroon (Sara Ngo Niobe - Eyangoh, Cristina Gutiérrez-Perez)
The study shows a recent epidemiological change of tubercle bacilli circulating in Cameroon. M. africanum represented more than 50% in 1970, but is currently isolated in less than 10% of cases. A highly prevalent genetic family of M. tuberculosis is recovered from approximately 40% of patients. This very homogenous family is also found in some other West African countries and in carabbean islands, tracing the slavery roads.
Taxonomy of tubercle bacilli (Cristina Gutiérrez-Perez, Véronique Vincent)
The definition of M. africanum has been revised in the light of newly described molecular markers, specially deleted regions identified in S. Cole's laboratory by genomic comparison of m. tuberculosis and M. bovis.
M. abscessus in cystic fibrosis (Véronique Vincent)
Our laboratory participates to a multicentric project for the determination of the incidence of mycobacterial infections in cystic fibrosis in children. A systematic search of mycobacteria in respiratory specimens has been initiated. M. abscessus is the main mycobacterial species involved in respiratory infections, detected in 5% of patients among approximately 10% of patients positive for mycobacteria. Molecular typing by pulsed-field gel electrophoresis shows the heterogeneity of strains and the absence of a common reservoir, specially nosocomial, and the absence of patient to patient transmission.
Interest of glycosylated proteins for the diagnosis of active tuberculosis (Gilles Marchal, Pascale Pescher, Félix Romain, Pierre Chavarot)
Tuberculosis diagnosis is difficult. Treatment is started whereas bacterial presence is detected in only 40% of cases. In our laboratory, we characterized antigens able to interact with cells (T lymphocytes), involved in the control of an experimental infection in guinea-pigs. These molecules are secreted during bacterial multiplication. Chemical analysis showed unique biochemical properties, with a high Proline content and the presence of glycosylated residues. Antigenic peptides are the glycosylated peptides. Purified molecules and synthetic peptides (in collaboration with Unité de Chimie organique) are recognised by lymphocytes from patients with active tuberculosis but not by lymphocytes from controls. This difference in the response of circulating lymphocytes, according to their source from patients or from contacts, will allow to develop a method for confirming active tuberculosis.
Interest of BCG in asthma treatment (Gilles Marchal, Pascale Pescher, Félix Romain, Pierre Chavarot, Micheline Lagranderie, Jean Lefort)
Asthma is a highly prevalent and serious health problem. In a murine experimental model of asthma, we studied the curative effect of BCG inactivated by freeze drying (EFD). After EFD-treatment, the parameters of asthma (airways eosinophilia and inflammation, bronchial hyperreactivity) were reduced.
Keywords: Tuberculosis, Epidemiology, Molecular typing, Immunodominant antigen, Mannosylation, Cystic fibrosis, Asthma