Mycobacterium cell wall

FIGURE 3.9 Libraries tested as inhibitors of enzymes involved in the biosynthesis of the mycobacterium cell wall. 

Korbelik, M. and Cecic, I., Enhancement of tumour response to photodynamic therapy by adjuvant mycobacterium cell-wall treatment, /. Photochem. PhotobioL B, 44, 151, 1998. 

Several methylated sugars have been identified in hydrolyzates of LPS, cell-wall polysaccharides, and extracellular polysaccharides. A considerable number of these have been found in the LPS from photosynthetic prokaryotes. Two polysaccharides from Mycobacterium species, a glucan" and a mannan" are remarkable in that they contain high percentages of methylated sugars. Glycolipids from Mycobacterium species are also rich in methylated sugars, some of which have not been found elsewhere, but this is beyond the scope of the present article. 

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. 

Nikaido H., Kim S.-H. Rosenberg E.Y. (1993) Physical organization of lipids in die cell wall of Mycobacterium chelonae. Mol Microbiol, 8, 1025-1030. 

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

Stahl, C., Kubetzko, S., Kaps, I., Seeber, S., Engelhardt, H. and Niederweis, M. (2001). MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis, Mol. Microbiol., 40, 451-464. 

Pathogens known to stimulate CSF production include Salmonella typhi-murium, Mycobacterium lepraemurium, Brucella abortus and Schistosoma mansonii. Additionally, non-viable bacteria or bacterial products, such as Nocardia rubra cell-wall fragments, muramyl peptides and bacterial endotoxins, can also induce CSF production. 

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. 

Pharmacoiogy Inhibits cell-wall synthesis in susceptible strains of gram-positive and gram-negative bacteria and in Mycobacterium tubercuiosis. 

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. 

Therapeutic vaccines were tested in BALB/c mice bearing TA3-Ha mammary carcinoma. The treatment consisted of 4 subcutaneous injections, at 3-6 days intervals, of Detox [a commercial preparation of cell wall skeletons from Mycobacterium phlei and non-toxic monophosphoryl lipid A from Salmonella minnesota (S. minnesota) in squalane oil and Tween 80 from Ribi Immunochemical research, Montana, USA] mixed with Thomsen-Friedenreich (TF) antigen coupled with KLH (Keyhole Limpet Hemocyanin) performed 5 days after the tumor cell injection. This vaccination achieved the survival of 25 % of the mice. Pretreatment of mice with cyclophosphamide in order to inhibit any suppressive response, increased survival to 50 % when the treatment began 5 days after tumor cell injection, and to 90 % when the treatment began 2 days after tumor cell injection. Both antibody as well as delayed-... 

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). 

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