Unit: Mycobacterium Reference
Director: Véronique Vincent
The role of environmental mycobacteria in human pathology has been investigated, specifically in AIDS patients in Ivory Coast, a country with high tuberculosis incidence. A European study showed epidemiological changes of mycobacterial flora in man, in common trends for all countries of the region. The study of biodiversity of tubercle bacilli in Africa identified a new genetic family of M. tuberculosis which recently emerged and is higly prevalent in Cameroon. Distinct genetic groups of M. africanum are identified in West and East Africa.
A glycoprotein produced during the bacterial growth has been characterized. A method for diagnosis of active tuberculosis, based on the lymphocyte T CD4+ responses toward the molecule is under a validation process
Mycobacterium National Reference Center (Gilles Marchal, Véronique Vincent, Cristina Gutiérrez-Perez, Annie Landier, 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. We participated to a comprehensive review of the role of environmental mycobacteria in human pathology. A national study is being perfomed for assessing the incidence and the role of environmental mycobacteria in cystic fibrosis.
Genetic biodiversity of tubercle bacilli in Africa (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 very homogeneous genetic family of M. tuberculosis is recovered from approximately 40% of patients. This higly prevalent family is also found in some other West African countries and in carabbean islands, tracing the slavery roads. The molecular epidemiology of M. africanum shows distinct homogeneous genetic groups in Wesrt and East Africa, with an on-going evolution of a specific sub-group in West Africa.
Role of environmental mycobacteria in human pathology (Cristina Gutiérrez-Perez, Véronique Vincent)
The role of environmental mycobacteria in human pathology has been studied in AIDS patients in a country with high tuberculosis prevalence ( Ivory Coast). In children pulmonary location was associated with adenopathies and digestive symptoms. In adults, the incidence of positive blood culture was 1.8/100 person-year.
Epidemiology of environmental mycobacteria (Véronique Vincent)
The epidemiolgy of M. kansasii in the United States, main agent of lung diseases in non-HIV patients and involved in disseminated diseases in AIDS patients, shows that a single clone is responsible for most cases, suggesting specific virulence factorsw associated with this genotype, and confirming similar data previously shown in France. A European study showed a recent increase of the incidence of M. avium and M. xenopi in clinical samples as well other epidemiological changes of the mycobacterial flora.
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, Mohammad Abolhassani)
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. A transfer of method to a pharmaceutical manufacturer is running to obtain samples which could be assayed on asthmatic patients.
Keywords: Tuberculosis, Environmental mycobacteria, Epidemiology, Molecular typing, Immunodominant antigen, Mannosylation, Asthma