ABC transporters influence sensitivity of Brugia malayi to moxidectin and have potential roles in drug resistance.

Some ABC transporters play a significant role in human health and illness because they confer multidrug resistance (MDR) through their overexpression. Compounds that inhibit the drug efflux mechanism can improve efficacy or reverse resistance. Of the eight described ABC transporter subfamilies, those proteins conferring MDR in humans are in subfamilies A, B, C, and G. In nematodes, transporters in subfamilies B and C are suggested to confer resistance to ivermectin. The Brugia malayi ABC transporter superfamily was examined to assess their potential to influence sensitivity to moxidectin. There was an increase in expression of ABC transporters in subfamilies A, B, C, and G following treatment. Co-administration of moxidectin with inhibitors of ABC transporter function did not enhance sensitivity to moxidectin in males; however, sensitivity was significantly enhanced in females and microfilariae. The work suggests that ABC transporters influence sensitivity to moxidectin and have a potential role in drug resistance.

Factors influencing lethality of Bacillus thuringiensis kurstaki toxin for eggs and larvae of Trichostrongylus colubriformis (Nematoda).

A toxin from Bacillus thuringiensis kurstaki was lethal to eggs and first- and second-stage larvae of the ruminant nematode Trichostrongylus colubriformis. Sheathed and exsheathed third-stage larvae were also killed by the toxin. However, susceptibility of the ova to the toxin decreased after several hours of development. Heating at 65 C for 1 hr or freezing at 0 C for 3 mo did not affect stability of the toxin. Ovicidal activity of the toxin was not altered by treatment with 13 microbial or mammalian enzymes, but toxicity was reduced by the antibiotics streptomycin or penicillin G and the enzyme inhibitor L-1-tosylamide 2-phenylethylchloromethyl ketone. Cuprous, ferrous, and zinc chlorides also inhibited the ovicidal activity of the toxin. Increased osmolarity of the assay media or solubilization of the toxin from pH 3 to 11 had no effect on toxicity for eggs. The membrane agents sodium vanadate and 4,4'-diisothiocyano-2,2' disulfonic acid stilbene increased (9-fold) and decreased (333-fold) toxicity, respectively. N-acetylneuraminic acid was the only tested sugar that reduced the toxicity of B. t. kurstaki.