Mycobacterium tuberculosis membrane

Mycobacteria such as Mycobacterium tuberculosis, Mycobacterium avium, Myco-bac-terium leprae, Mycobacterium kansasii, Mycobacterium fortuitum-M, Mycobacterium chelonae, and a few others are pathogenic organisms that cause very serious diseases in humans. The characteristic feature of mycobacteria is their high content of lipids (about 40% of their mass), and they are primarily located on the outer bacterial membrane. 

Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycoUc acid, an important component of the cell membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the cause of the selective toxicity of the drag with respect to these microorganisms. 

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

Gu S, Chen J, Dobos KM et al (2003) Comprehensive proteomic profiling of the membrane constituents of a Mycobacterium tuberculosis strain. Mol Cell Proteomics 2 1284-1296... 

Figure 1 Physical and chemical stimuli affecting the gating of bacterial MS channels. (A) The structure of the pentameric MscL channel (left) and a channel monomer (right) from Mycobacterium tuberculosis according to the 3-D structural model of a closed channel (7). MscL is activated by membrane stretch, amphipaths (e.g., lysophopholipids, chlorpromazine, and trinitrophenol) and parabens. The channel activity is inhibited by Gd + and static magnetic fields (SMF) and is modulated by temperature and intracellular pH (3). (B) The structure of the MscS heptamer (left) and the channel monomer (right) from E. coli based on the 3-D structural model of MscS (8) most likely depicting an inactive or desensitized functional state of the channel (3). MscS is activated by membrane stretch, amphipaths, and parabens and is modulated by voltage. The activity of the channel is inhibited by Gd + and high hydrostatic pressure (HHP) (3). The arrows point at membrane structures (i.e., channel protein and/or lipid bilayer) affected by the specific stimuli.

D-arabinogalactan of Mycobacterium tuberculosis is known to involve conversion of 5-phosphoribosyl-ot-pyrophosphate to 5-phospho-(3-ribosyldecaprenyl phosphate by a membrane-bound enzyme, which has been cloned, sequenced and functionally expressed. The sugar attached to the decaprenyl glycosyl donor (not dolichol, since the sugar-proximal prenyl unit is not reduced) is then... 

Vrljic et al. cloned a new gene lysE from Corynebacterium glutamicum and showed that it encodes the translocator which specifically exports L-lysin out of the cell [10]. Recently they analyzed the membrane topology of the gene product and showed that it is a member of a family of proteins found in some bacteria -Escherichia coli, Bacillus subtilis, Mycobacterium tuberculosis, and Helicobacter pylori. The authors suggested that LtsE superfamily members will prove to catalyze the export of a variety of biologically important solutes including amino acids [11-13]. 

The FabH proteins play a major role in specifying product diversity. E. coli FabH is specific for acetyl-CoA as the primer and this organism makes only straight-chain, even-numbered fatty acids. The FabH from gram-positive bacteria that produce branched-chain fatty acids are selective for five- and seven-carbon branched-chain precursors derived from amino acids. In Mycobacterium tuberculosis, the FabH prefers long-chain fatty acids and this organism is characterized by the presence of very long-chain mycolic acids in the membrane. 

Subsequent research led to the discovery that p-aminosalicylic acid (PAS) was an active antitubercular agent, and it was suggested that the antitubercu-lar activity of this drug was due to its Cu(II) complex [526], which was prepared and found to be 10-times as active as PAS itself [527]. Studies of Cu(II)(4-aminosalicylate)2 also revealed that it was 30-times more lipid-soluble than PA [528, 529]. The enhanced activity of the copper complex was attributed to this increased lipid solubility, which facilitated penetration of the fatty outer membrane of Mycobacterium tuberculosis. 

Although we have tried periodically over the years, we have thus far been unable to demonstrate a physical association of intracellular arsenate reductase with membrane ArsB transport protein (S. Silver and B. P. Rosen, unpublished data). The recently released entire 4.4-million-base-pairs genome of Mycobacterium tuberculosis (56), the cause of the major human disease, includes among... 

Fratti, R.A., Vergne, L, Chua, J., Skidmore, J., and Deretic, V. 2000, Regulators of membrane trafficking and Mycobacterium tuberculosis phagosome maturation block. Electrophoresis 21 3378-3385. 

Recent applications of solid state NMR to membrane protein characterisation also include the light-harvesting complex II of Rhodopseudomonas acidophila", glycinated mastoparan-X , diacylglyerol kinase from E. coli" phospholamban , Rv2433c from Mycobacterium tuberculosis and the ABC transporter LmrA from Lactococcus lactis". ... 

Valinomycin cyclo-(-D-Val-Lac-Val-D-Hyv-)j, an antibiotic, cyclic depsipeptide, especially active against Mycobacterium tuberculosis. In addition to valine, it contains the heterocomponents, L-lactic acid (Lac) and n-a-hydroxyisovaleric acid (o-Hyv). It is an lonophore (see), which selectively transports potassium ions across membranes. 

Structure of the cell wall membrane of Mycobacterium tuberculosis... 

Three-dimensional backbone structure of Rvl761c from Mycobacterium tuberculosis has been characterized using dodecylphosphocholine micelles as a membrane mimetic... 

Other NMR applieations to integral membrane proteins include the expression, purification and NMR characterization of the integral membrane proteins RvOlSOc and Rv3004c from Mycobacterium tuberculosis, and an E.coli integral membrane protein investigated by solid state NMR. ... 

The chemistry and immunostimulant properties of the cell walls of mycobacteria and related organisms have been reviewed. Concanavalin A has been shown to react with three antigenic polysaccharides present in culture filtrates of Mycobacterium tuberculosis, these polysaccharides were isolated by direct precipitation and affinity chromatography. A mannan esterified with succinic acid has been isolated from extracts of mesosomal and plasma membranes of Micrococcus lysodeikticus The polysaccharide was precipitated by concanavalin A, but it was attacked only slightly by jack-bean a-mannosidase. I.r. spectroscopy indicated the presence of both esterified and free carboxy-groups in the mannan. Mesosomal membranes isolated from M. lysodeikticus, unlike preparations of plasma membranes, were unable to catalyse the incorporation of D-[ C]mannose from GDP-D-[ C]mannose into the mannan it appears that the membrane system is unable to synthesize the carrier lipid undecaprenyl D-mannosyl phosphate. It was suggested that the juxtaposition of the mesosomal vesicles and the enveloping plasma membrane in vivo allows the mannan located on the mesosomal vesicles to accept D-mannosyl units from the carrier lipid located in the plasma membrane. 

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