AN EFFECTIVE NEW DRUG TARGET FOR THE TREATMENT OF TUBERCULOSIS

The present invention allows a screening method for identifying novel drugs for the treatment of tuberculosis as well as a diagnostic method for identifying clinical strains that are resistant to these novel drugs

NITROREDUCTASE NfnB FROM Mycobacterium smegmatis

The present invention relates to a screening method for the identification of new nitrobenzothiazinone drugs for the treatment of tuberculosis, which are not or are slowly transformed and inactivated by nitroreductase. The use of the nitroreductase NfnB from M. smegmatis in cancer therapy, and in bioremediation are comprised as well

Genomic analysis of zinc homeostasis in Mycobacterium tuberculosis

Zn is involved in several cellular processes and the maintenance of cellular Zn status is essential for life. Therefore, an improved understanding of zinc acquisition and metabolism is of great significance, especially in important pathogens such as Mycobacterium tuberculosis whose capacity to survive within the phagosomal compartment is fundamental for its pathogenicity. A crucial point is the bacterial ability to compete with the host for nutrients, and the acquisition of metal ions, such as iron and zinc

Rv2686c-2687c-2688c, an ABC fluoroquinolone efflux pump from Mycobacterium tuberculosis

The Mycobacterium tuberculosis Rv2686c-Rv2687c-Rv2688c operon, encoding an ABC transporter, conferred resistance to ciprofloxacin and, to a lesser extent, norfloxacin, moxifloxacin, and sparfloxacin to Mycobacterium smegmatis. The resistance level decreased in the presence of the efflux pump inhibitors reserpine, carbonyl cyanide m-chlorophenylhydrazone, and verapamil. Energy-dependent efflux of ciprofloxacin from M. smegmatis cells containing the Rv2686c-Rv2687c-Rv2688c operon was observed

Design, synthesis and evaluation of new GEQ derivatives as inhibitors of InhA enzyme and Mycobacterieumtuberculosis growth

International audienc

Glutamine amidotransferase activity of NAD+ synthetase from Mycobacterium tuberculosis depends on an amino-terminal nitrilase domain.

NAD+ synthetase (NadE; E.C. 6.3.5.1) from Mycobacterium tuberculosis utilizes both glutamine and ammonia to catalyze NAD+ production, in contrast to the corresponding NH3-dependent enzymes from other prokaryotes. Here we report the site-directed mutagenesis of amino acids located in the N-terminal domain and predicted to be essential for glutamine hydrolysis. The residues forming the putative catalytic triad (Cys176, Glu52 and Lys121) were replaced by alanine; the mutated enzymes were expressed in the Escherichia coli Origami (DE3) strain and purified. The three mutants completely lost their glutamine-dependent activity, clearly indicating that Cys176, Glu52 and Lys121 are crucial for this activity. In contrast, the C176A and E52A variants, respectively, retained 90 and 30% of the original NH3-dependent specific activity, while the K121A mutant lost this activity. The results show that glutamine-amidotransferase activity is mediated by an N-terminal domain belonging to the superfamily of nitrilases. This domain, a new type of glutamine amide transfer (GAT) domain, is the first to be characterized in bacterial NAD+ synthetases