Mycobacteria cord factor

Bacteria also contain a very rich variety of glycolipids with unusual structures. Lipid A13 is the site of attachement of the 0-specific chain of Gram (-) bacteria, which constitutes the antigenic lipopolysaccharide [87]. Other members of this family can be quoted, for example glycosyl glycerophospholipids in which the carbohydrate and glycerol moieties are linked by a phosphodiester bond (e.g. GPI anchor 14) [88] or carbohydrate esters (e.g. cord-factor of mycobacteria 15). 

As concerns the chemistry of these glycolipids, they contain either an eater linkage between the sugar moiety and the lipid moiety, as in cord factor and in wax D of Mycobacteria, or they are glycosides of phenolic alcohols (as in mycoside B) or of inositol (as in the phosphoglycolipids), or they can be linked to the carboxyl group of D-alanine (as in mycoside C). 

A toxic lipid isolated by Spitznagel and Dubos by extraction of Mycobacteria with monochlorobenzene has been shown to contain cord factor as the only active compound. ... 

The chemistry of cord factor, a toxic lipid of virulent or attenuated Mycobacteria has already been described in detail (see p. 210). It has also been mentioned that at least part of this biological activity can be explained by the action of cord factor on dehydrogenases dependent on diphospho-pyridine nucleotide as described by Kato and coworkers (see p. 231). 

Cord Factor Trehalose 6,6-dimycolaie 6.6 -di-0-mycolyl -a,a-trehalose (6-O-mycolyl -dr-D-glucopyranos-yl) 6-0 mycolyl-ot-D-glucopyranoside Toxic glycolipjds responsible for the cord formation and the leukotoxic effect of virulent bacilli. The term cord factor is widely used for the natural mixture of trehalose dimycolates produced by virulent Mycobacteria, Nocardia, Corynebacteria and attenuated BCG, q.v. For precise designation, the strain from which the preparation was isolated must be mentioned. First isolated from Mycobacterium tuberculosis H. Bloch, J. Exp. 

The cell walls of M. lepraemurium have been harvested from the livers of moribund rats that had been infected with the above organism. The walls contained a cord factor (oa-trehalose-6,6-dimycolate) that was similar in structure to the well-characterized cord factor from M. tuberculosumThis is the first unequivocal identification of a cord factor as a product of in vivo derived mycobacteria. 

An important example of a carbohydrate ester is the so-called cord factor from Mycobacteria spp. This contains an ester of the disaccharide, trehalose, with two molecules of a complex acid, mycolic acid. The latter is a general term embracing a whole series of fatty acids containing 60-90 carbons. They are hydroxy fatty acids which differ in their degree of unsaturation and chain branching (Section 1.9). In the example given in Fig. 2.6 the mycolic acid is the 60-carbon compound found in Mycobacterium smeg-matis. 

In addition to the wall-bound mycolic acids three other important lipids are loosely associated with the murein layer. The st of these is the cord factor , so called since it was associated with the formation of cords , parallel rows forming characteristic serpentine strands demonstrable when smears of liquid grown cultures of mycobacteria are examined under the microscope. The cord factor of M. tuberculosis can be readily extracted from viable bacteria with organic solvents and identified as trehalose-6,6 -dimycolate. The mycosides constitute the second group of readily extractable lipids, gycosidically linked to the para position of a phenol... 

Infection with mycobacteria appears to stimulate the immunity of the host to tumours. Isolated cell walls also provide some antitumour activity but treatment with proteolytic enzymes or organic solvents destroys the tumour-suppressive properties of the walls. Subsequent addition of cord factor restores this activity. 

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