Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306

Novel mycoloyl glycolipids with short carbon chains were isolated and purif ied from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chem ical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalo se 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fruct ose 8-monomycolate. The length of carbon chains and number of double bonds Of mycolic acids were C-34, C-36 and C-38 saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tube rculosis (C78-88 monoenoic and dienoic). Among them, only. TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By co ntrast, other mycoloyl glycolipids induced mild lesions. The small-sized TD M of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed; of mycolic acid with the shortest carbon chains, when compared to granulom atogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously . Our results imply that rhodococcal TDM is a pathogenetic factor similar t o that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity. (C) 2001 Academic Press.