The persistence of numerous pathogenic bacteria important in disease states, such as tuberculosis, in humans and domestic animals has been ascribed to an inhibition of fusion between the phagosomal vesicles containing the bacteria and lysosomes in the host cells [Elsbach, P. & Weiss, J. (1988) Biochim. Biophys. Adia 974, 29-52; Thoen, C. 0.(1988)J. Am. Vet. Med. Assoc. 193, 1045Assoc. 193, -1048. In tuberculosis this effect has been indirectly attributed to the production of cord factor (a,a-trehalose 6,6'-dimycolate). We show here that cord factor is extraordinarily effective at inhibiting Ca2+-induced fusion between phospholipid vesicles and suggest a mechanism by which cord factor confers this effect. These findings are likely to be important in our understanding of the pathogenesis and treatment of many diseases of bacterial etiology.

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"Cord factors" are diesters of a,a-trehalose produced by Mycobacteriae and Corynebacteriae. Saponification of the "cord factor" of Corynebacterium diphtheriae gives an equimolecular mixture of homologues of the saturated corynomycolic and of the unsaturated corynomycolenic acids (I and 11, R = H). Mass spectrometry of their methyl esters confirms their structures (see Fig. 1 ,The peracetylated cord factor (IV, a, b, c) gave very weak molecular ions at m/e 1630, 1632 and 1634 showing apparently that it is a mixture of the diesters having respectively two saturated, one saturated and one unsaturated, and two unsaturated acyl radicals. Strong peaks a t mle 809 and 807 are attributed to the oxonium ions (V a and V b).These results as well as chemical degradations show that the "cord factor" of C. diphtheriae is a mixture of glycolipids (I11 a, b, c). La permethylation du glycolipide, ainsi que l'identification du tri-0-methyl glucose (effectukes par M. Yamakawa) ont Bt6 faites essentiellement selon No11 et coll. [S]. AcktylationEnviron 3 m g de substance, en solution dans 0,5ml de pyridine sont gard6s pendant une nuit apres addition de 0,5 ml d'anhydride ac6tique. Aprks Bvaporation B sec sous vide, environ 0,1 mg du residu a Bt6 utilise directement pour la spectrometric de masse. XpectromCtrie de rnasse