Mycobacterium infections of the Mycobacterium tuberculosis complex in Libreville : profile of resistance to antibiotics and genetic diversity ; Les infections à mycobactéries du complexe Mycobacterium tuberculosis à Libreville : profil des résistances aux antibiotiques et diversité génétique

The emerging phenomenon of the MDR and XDR-TB is a worldwide public health issue. In developing countries, this problem is amplified due to the fact that TB diagnostic laboratories lack equipment and diagnostic tools to identify these cases and therefore prescribe appropriate chemotherapy. In the first part of this doctoral work, the sequencing of the pncA gene allowed us to show that the resistance to Pyrazinamide occurs significantly when the strain is MDR, corresponding to the acquisition of resistance to Rifampicin and Isoniazid; and that after the acquisition of Fluoroquinolones and to injectable antibiotics of second line (Amykacine, Kanamycine, Capreomycine) resistance by MDR strains, this rate increases even more. In the second part of the study, we propose an alternative method to the culture of bacilli in a BSL3 confined environment. From uncultivated clinical samples (sputum) and through GeneXpert MTB/RIF, sequencing of genes and spoligotyping, we identified 19 MDR strains, active transmission of sensitive strains belonging to clades LAM10, T1, MANU, H3 and finally as well as an underlying epidemic of 5 Beijing MDR strains.In the first study, 272 retrospective samples of Mycobacterium tuberculosis isolates were selected from two large cosmopolitan cities: Northern Paris (Bichat-Claude Bernard Hospital, 101 strains) and Southwest of Shanghai (Songjiang district, 171 Strains). These strains were selected according to their known phenotypic sensitivity to Rifampicin (RIF) and Isoniazid (INH). These phenotypic resistances were confirmed by the HAIN genotype analysis tools MTBDRplus and by the sequencing of the rpoB and katG/inhA genes. To determine the extensively drug resistance strains (XDR), we sequenced the gyrA/gyrB and rrs genes to identify genetic mutations associated with resistance to Fluoroquinolones (FQs) and second-line injectable antibiotics: Amikacin (AMK)-Kanamycin ( KAN)-Capreomycin (CAP), respectively. Finally, we sequenced the pncA gene of all isolates to identify the genetic mutations ...