BAFILOLIDES, POTENT INHIBITORS OF THE MOTILITY AND DEVELOPMENT OF THEFREE-LIVING STAGES OF PARASITIC NEMATODES

Three Streptomyces isolates were identified as producing macrolide ant ibiotics of the bafilomycin or leucanicidin types during an evaluation of Australian actinomyces for the production of inhibitors of larval development in the parasitic nematode, Haemonchus contortus, Bafilomyc ins A(1), B-1, C-1, and D were obtained from culture A239 and the 2-O- methyl-L-rhamnosyl derivative of bafilomycin A(1), leucanicidin, from cultures A223 and A240, All these 'bafilolides' gave similar patterns of inhibition typified by an initial paralysis of newly hatched L(1) l arvae and a lethal toxicity within 24 h, LD(50) values for inhibition of larval development of McMaster H. contortus ranged from 0.23 mu g m l(-1) for leucanicidin to 2.5 mu g ml(-1) for bafilomycin D, The bafil olides had broad spectrum nematocidal activity, being equi-potent as i nhibitors of H. contortus, Trichostrongylus colubriformis and Ostertag ia circumcincta larval development, Further, all bafilolides caused so me inhibition of H. contortus L(3) motility, with the semi-synthetic a nalogue, bafilomycin B-2, the most potent inhibitor (LP(50) against Mc Master H. contortus 1.9 mu g ml(-1)). Nematode strains resistant to th e known benzimidazole, levamisole and avermectin anthelmintics showed no cross resistance to the bafilolides, supporting the hypothesis that the bafilolides act by an independent mechanism.