J Biol Chem
February 2003
Disruption of the mma4 gene (renamed hma) of Mycobacterium tuberculosis has yielded a mutant strain defective in the synthesis of both keto- and methoxymycolates, with an altered cell-wall permeability to small molecules and a decreased virulence in the mouse model of infection (Dubnau, E., Chan, J., Raynaud, C.
View Article and Find Full Text PDFExperimental observations, accumulated during several decades, have allowed an overall scheme for the biosynthesis of the mycolic acids, which are very long chain fatty acids of Mycobacteria to be proposed. But, in almost every step, several hypotheses are compatible with the experimental results, leading to variations of the overall scheme. The aim of this review is to point to some additional possibilities.
View Article and Find Full Text PDFMost drug-resistant clinical isolates of the tubercle bacillus are resistant to isoniazid, a first-line antituberculous drug. This antibiotic was shown to act on Mycobacterium tuberculosis by inhibiting a 2-trans-enoyl-acyl carrier protein reductase, called InhA. However, the exact role played by InhA in mycobacteria remained unclear.
View Article and Find Full Text PDFMycobacteria are known to acquire resistance to the antituberculous drug pyrazinamide (PZA) through mutations in the gene encoding pyrazinamidase (PZase), an enzyme that converts PZA into pyrazinoic acid, the presumed active form of PZA against bacteria. Additional mechanisms of resistance to the drug are known to exist but have not been fully investigated. Among these is the non-uptake of the pro-drug, a possibility investigated in the present study.
View Article and Find Full Text PDFMycobacterial lipids have been studied for more than 70 years, due to the fascinating diversity of their structures and biological activities. A historical perspective, and the present status on the structure and activity of major lipids of the outer envelope of mycobacterial cells are presented : mycolic acids, which are main constituents of the cell wall, and glycolipids known for toxic or immunological properties (cord factor, SL, DAT, PGL, GPL, LOS, LAM). As far as possible, it was tried to distinguish between experimentally established knowledge and currently accepted speculations.
View Article and Find Full Text PDF