Three Streptomyces isolates were identified as producing macrolide antibiotics of the bafilomycin or leucanicidin types during an evaluation of Australian actinomyces for the production of inhibitors of larval development in the parasitic nernatode, Haemonchus contortus. Bafilomycins A1, B1, C1, and D were obtained from culture A239 and the 2-O-methyl-l-rhamnosyl derivative of bafilomycin A1, leucanicidin, from cultures A223 and A240. All these 'bafilolides' gave shuilar patterns of inhibition typified by an initial paralysis of newly hatched L1 larvae and a lethal toxicity within 24 h. LD50 values for inhibition of larval development of McMaster H. contortus ranged from 0.23 μg ml-1 for leucanicidin to 2.5 μg ml-1 for bafilomycin D. The bafilolides had broad spectrum nematocidal activity, being equi-potent as inhibitors of H. contortus, Trichostrongylus colubriformis and Ostertagia circumcincta larval development. Further, all bafilolides caused some inhibition of H. contortus L3 motility, with the semi-synthetic analogue, bafilomycin B2, the most potent inhibitor (LP50 against McMaster H. contortus 1.9 μg ml-1). Nematode strains resistant to the known benzimidazole, levamisole and avermectin anthelmintics showed no cross resistance to the bafilolides, supporting the hypothesis that the bafilolides act by an independent mechanism.
- natural product