| Abstract: | Experimental evidence indicates that tubulin is the site of action of the anthelmintic benzimidazoles. Furthermore, certain residues of β-tubulin seem to be critical for this mechanism. Although the benzimidazoles selectively affect nematode vs. mammalian β-tubulin, the molecular basis for this differential action is not known. To enhance our understanding of this phenomenon, and to provide the basis for investigating benzimidazole resistance in parasitic nematodes, we undertook the cloning of β-tubulin cDNAs from the ruminant parasite, Haemonchus contortus. We have cloned and sequenced three β-tubulin cDNAs from this organism, β12–16, β12–164, and β8–9. The first 2 differ at only 23 nucleotides, which give rise to 4 amino acid changes, β8–9 represents a different isotype class from the other two, since it differs extensively in the carboxyterminus. By comparing the sequences of these and other nematode β-tubulins with mammalian β-tubulins, several regions of consistent difference can be recognized; the functional significance of these regional differences has not been defined. Sequences very similar or identical to β8–9 and β12–16 are present in both benzimidazole-sensitive and benzimidazole-resistant populations of H. contortus. However, it appears that drug-resistant organisms may differ in the presence of a gene product which is closely related to β8–9. |
