Mycobacteria cell wall polysaccharides

In the previous edition of this book, Todd Lowary exhaustively reviewed what was known to date about the structure, function and bios)uithesis of the mycobacterial cell wall polysaccharides, as well as chemical syntheses of substrates and inhibitors for the biosynthetic enzymes [21]. Cell wall biosynthesis remains better studied in mycobacteria than in the other mycolata because of the obvious medical significance of these bacteria. The purpose of this section is therefore to highlight more recent developments in the study of the mycobacterial cell wall, and to describe some of the variation in cell wall stmcture seen among different genera within the mycolata. 

A branched-chain AG, with the Ara residues forming the nonreducing termini, was recognized as the major cell-wall polysaccharide in mycobacteria in the middle of the last century and numerous excellent reviews have... 

The chemical compositions of cell-wall polysaccharides of mycobacteria have been ably reviewed. ... 

The cell walls of mycobacteria contain three structures peptidoglycan, an arabinogalactan polysaccharide and long chain hydroxy fatty acids (mycolic acids) which are all covalently linked. Additional non-covalently attached lipid components found in the wall include glycolipids, various phospholipids and waxes. The lipid-rich nature of the mycobacterial wall is responsible for the characteristic acid-fastness on staining and serves as a penetration barrier to many antibiotics. Isoniazid and ethambutol have long been known as specific antimycobacterial agents but their mechanisms of action have only recently become more clearly understood. 

Several studies concerning D-mannosyl transfer from GDP-Man and Man-p-Pre onto unidentified acceptors in Mycobacteria have been published.67,393 The enzymic system may use methyl a-D-mannopyranoside as the exogenous acceptor for D-mannosyl transfer.394 In this case, formation of a-(l- 2) linkages was observed they are present in 3-O-methyl-D-mannose-containing polysaccharides and a D-arabino-D-mannan characteristic of mycobacterial cell-wall. 

Recent interest in oligoarabinans, have been triggered by their presence in the lipoarabinoman-nan polysaccharide component of the cell wall complex of mycobacteria [85]. Several research groups have employed -pentenyl arabinofuranosides in their approaches to oligoarabinans. 

Fungal cell walls contain n-alkanes similar to those in the higher plants and possibly fulfilling a similar role. In contrast, waxes are absent in most bacteria. However, the mycobacteria and the related nocardiae and corynebacteria, which contain greater amounts of lipids than other types of bacteria, contain high-molecular-weight waxy molecules in their cell walls (Harwood Russell 1984).These molecules comprise various mycolic acids, such as P-mycolic acid (Fig. 2.15a), which are bonded to polysaccharides and, via phosphate groups, to murein (Fig. 2.9). 

Isoniazid is bacteriostatic for resting bacilli but bactericidal for dividing microorganisms. Isoniazid is a prodrug that is converted by mycobacterial catalase-peroxidase into an active metabolite. It inhibits biosynthesis of my colic acids—long, branched lipids that are attached to a unique polysaccharide in the mycobacterial cell wall. Mycolic acids are unique to mycobacteria. The target of the isoniazid derivative is enoyl-ACP reductase of fatty acid synthase II, which converts unsaturated to saturated fatty acids in mycolic acid biosynthesis. 

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. 

Figure 1. The structure of the polysaccharide components of the cell wall of Mycobacteria tuberculosis.

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