Mycobacterium tuberculosis, cell wall

Ma Y, Stern RJ, Scherman MS, Vissa VD, Yan W, Jones VC, Zhang F, Franzblau SG, Lewis WH, Mcneil MR. Drug targeting Mycobacterium tuberculosis cell wall synthesis genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose. Antimicrob. Agents Chemother. 2001 1407-1416. 

M.S. Scherman, K.A. Winans, R.J. Stern, V. Jones, C.R. Bertozzi, M.R. McNeil, Drug targeting mycobacterium tuberculosis cell wall synthesis development of a microtiter plate-based screen for UDP-galactopyranose mutase and identification of an inhibitor from a uridine-based library, Antimicrob. Agents Chemother. 2003, 47, 378-382. 

F. Zhang, S.G. Franzblau, W.H. Lewis, M.R. McNeil, Drug targeting Mycobacterium tuberculosis cell wall synthesis Genetics of dTDP-Rhamnose synthetic enzymes and... 

Gobin, J. Horwitz. M.A. Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall. J. Exp. Med. 1996. 183. 1527-1532. 

Mycobacterium tuberculosis is the causal organism of tuberculosis in humans. Allied strains cause infections in animals, e.g. bovine tuberculosis and tuberculosis in rodents. Due to the waxy nature of the cell wall this organism will resist desiccation and will survive in sputum. Tuberculosis has been largely eliminated by immunization and chemotherapy. 

The Lipoarabinomannan Components of the Cell Wall Complex of Mycobacterium tuberculosis NPOEs in Chemoselective, Regioselective and Three-Component Double Differential Clycosidations... 

Mycobacterium is a genus of bacteria that has characteristic cell walls and unusual staining properties. AIDS patients are most commonly infected with an atypical form of tuberculosis bacterium called Mycobacterium avium inter-cellulare. This bacterium does not normally cause disease in healthy people, but in AIDS patients, it may cause tuberculosis-like disease in the lungs. The infection can also involve numerous other tissues, such as the bone marrow, and bacteria may be present in the blood at very high levels. Patients with this opportunistic infection will have fevers and low number of white blood cells. These infections are often resistant to drugs. 

Pharmacology Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels, isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. 

Pharmacology Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. 

Ethambutol is a water-soluble, heat-stable compound that acts by inhibition of arabinosyl transferase enzymes that are involved in cell wall biosynthesis. Nearly all strains of M tuberculosis and M. kansasii and most strains of Mycobacterium avium-intracellulare are sensitive to ethambutol. Drug resistance relates to point mutations in the gene (EmbB) that encodes the arabinosyl transferases that are involved in mycobacterial cell wall synthesis. 

Susceptible strains of Mycobacterium tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1-5 mcg/mL. Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. Resistance to ethambutol is due to mutations resulting in overexpression of emb gene products or within the embB structural gene. 

BCG is a viable strain of Mycobacterium bovis that has been used for immunization against tuberculosis. It has also been employed as a nonspecific adjuvant or immunostimulant in cancer therapy but has been successful only in intravesical therapy for superficial bladder cancer. BCG appears to act at least in part via activation of macrophages to make them more effective killer cells in concert with lymphoid cells in the cellular efferent limb of the immune response. Lipid extracts of BCG as well as nonviable preparations of Corynebacterium parvum may have similar nonspecific immunostimulant properties. A chemically defined derivative of the BCG cell wall, [Lys18]-muramyl dipeptide, has been licensed in Japan to enhance bone marrow recovery after cancer chemotherapy. 

Mycobacterium tuberculosis, Mycobacterium leprae Pathogens Label-free Cell wall and membrane subproteomes (193-195)... 

The purpose of this chapter is to describe the competition for iron between iron-binding proteins of the animal and the siderophores of bacterial parasites. This discussion will be limited to two bacterial species—a slow-growing organism Mycobacterium tuberculosis and a fast-growing organism Escherichia coli. Both organisms produce specific siderophores which have been defined chemically and physically. Myco-bactin, the siderophore of M. tuberculosis, because of its hydrophobic nature, is associated mostly with the lipoidal cell wall of the tubercle bacillus (11) whereas enterochelin (enterobactin), the siderophore of E. coli and Salmonella typhimurium, is soluble in water and is rapidly lost by the bacterial cell into the surrounding medium (12, 13). 

Brennan, P.J., 2003, Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis Si 91-97. 

The compounds prepared were tested for their inhibitory activity against Mycobacterium tuberculosis glutamine synthetase (MtGS), an enzyme that plays a key role in mycobacterial cell-wall biosynthesis and nitrogen metabolism. Compound... 

The flavoenzyme UDP-galactop)ranose mutase (UGM) plays a key role in the cell wall biosynthesis of many pathogens, including Mycobacterium tuberculosis. McNeil and co-workers developed a microtiter plate assay for UGM (O Scheme 14) [157]. The assay is based on the release of tritiated formaldehyde from UDP-galactofuranose but not UDP-galactopyranose by periodate and was used to identify a uridine-based enzyme inhibitor from a chemical library. The potent inhibitor 320KAW73 (IC50 = 6 pM) was identified. 

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