Trehalose 6,6 -dimycolate

Mycobacterial components, e.g. trehalose dimycolate (TDM), muramyl dipeptide (MDP)... 

Aluminium phosphate, AIPO4 Aluminium hydroxide, Al(OH)3 Alum, A1K(S04)2.12H20 Calcium phosphate, CaP04 Mycobacterial species Mycobacterial components (e.g. trehalose dimycolate, muramyl dipeptide) Corynebacterium species Bordetella pertussis Lipopolysaccharide... 

Fractionation of mycobacteria resulted in the identification of two cellular immunostimulatory components, trehalose dimycolate (TDM) and muramyl dipeptides (MDP). Both are normally found in association with the mycobacterial cell wall. TDM is composed of a molecule of trehalose (a disaccharide consisting of two molecules of a-D-glucose linked via an a 1-1 glycosidic bond), linked to two molecules of mycolic acid (a long-chain aliphatic hydrocarbon-based acid) found almost exclusively in association with mycobacteria. TDM, while retaining its adjuvanticity, is relatively non-toxic. 

When crude endotoxin from the heptose-less mutant of Salmonella typhimurium is combined with trehalose dimycolate from mycobacteria in oil droplets and injected directly into established tumors (line 10 hepatocellular carcinoma) in syngeneic guinea pigs, rapid regression of the tumors occurs and over 90% of the animals are cured. The three required components for activity in this tumor model are (a) the endotoxin (b) the mycobacterial adjuvant, trehalose dimycolate and (c) a compound satisfying the minimal structural requirement (muramyl dipeptide) for adjuvant activity by bacterial cell wall materials. The mycobacterial cell wall skeleton is able to replace the latter two components. 

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. 

Trehalose dimycolate is now being marketed for the treatment of cancer in horses, by Ribi Immunochem Research, Hamilton, Montana. 

McLaughlin, C. A., S. M. Schwartzman, B. L. Horner, G. H. Jones, J. G. Moffatt, J. J. Nestor Jr., and D. Tegg Regression of tumors in guinea pigs after treatment with synthetic muramyl dipeptides and trehalose dimycolate. Science 208, 415 (1980). 

Tenu, j. P., E. Lederer, and J. F. Petit Stimulation of thymocyte mitogenic protein secretion and of cytostatic activity of mouse peritoneal macrophages by trehalose dimycolate and muramyl dipeptide. Eur. J. Immunol. 10, 647 (1930). 

We have shown earlier that the toxicity of endotoxin can be prevented to a large extent by antagonists of ADP-ribose metabohsm (1). On the other hand there are some indications that muramyldipeptide (MDP) interferes with the this metabolism also (2). It was reported in 1980 that MDP, in combination with trehalose dimycolate, could induce resistance against influenza viras infection (3). In this chapter we are dealing with the influence of muramyldipeptide and benzamide upon the mouse hepatitis virus type 3 (MHV3). 

Rapp P, Bock H, Wray V, Wagner F (1979) Formation, isolation and characterization of trehalose dimycolates from Rhodococcus erythropolis grown on n-alkanes. J Gen Microbiol 115 491-503... 

Methylation and subsequent hydrolysis of a,a-trehalose or /3,/3-trehalose produces two moles of 2,3,4,6-tetra O-methyl-D-glucose. Furthermore, methylation of a,a-trehalose 6,6 -dimycolate (see Section II, 2) and saponification of the resulting product to give hexa-0-methyl-a,a-trehalose, followed by hydrolysis, affords 2,3,4-tri-O-methyl-D-glucose (identified by paper chromatography and periodate oxidation). 

In Mycobacteria, trehalose occurs not only as the free sugar but also as a component of various glycolipids, such as trehalose 6,6 -dimycolate. 

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. 

The 6,6 -dimycolates of Trehalose are present as mixtures in Mycobacterium tuberculosis and other microorganisms. Sol. CHCI3, hexane. 

Trehalosamine, T-122 a,a-Trehalose 6,6 -dimycolate, T-126 a,p-Trehalose Octa-Ac, T-124 P,p-Trehalose Octa-Ac, T-125 P,p-Trehalose Octa-Me, T-125 a,a-Trehalose, T-123 a,p-Trehalose, T-124 p,p-Trehalose, T-125... 

The structure of the cord factor from Mycobacterium smegmatis has been confirmed as (j ,a trehalose 6,6 -dimycolate (CieeHajsOis). The a,a trehalose was identified by paper chromatography and the positions of ester linkages at 0-6 and 0-6 was established by C n.m.r. spectroscopy. 

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... 

Hsu, RR, Wohhnann, J., Turk, J. and Haas, A. (2011) Structural definition of trehalose 6-monomycolates and trehalose 6,6 -dimycolates from the pathogen Rhodococcus equi by multiple-stage hnear ion-trap mass spectrometry with electrospray ionization. J. Am. Soc. Mass Spectrom. 22, 2160—2170. 

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