Cord factor (alpha,alpha-trehalose 6,6'-dimycolate) inhibits fusion between phospholipid vesicles

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. Acta 974, 29-52; Thoen, C. O. (1988) J. Am. Vet. Med. Assoc. 193, 1045-1048]. In tuberculosis this effect has been indirectly attributed to the production of cord factor (alpha,alpha-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.