glutamate-gated chloride channels of haemonchus contortus restore drug sensitivity to ivermectin resistant caenorhabditis elegansglutamate-gated氯通道的haemonchus contortus恢复伊维菌素抗线虫的药物敏感性.pdfVIP

Glutamate-Gated Chloride Channels of Haemonchus contortus Restore Drug Sensitivity to Ivermectin Resistant Caenorhabditis elegans 1 2 3 1 Susan K. Glendinning , Steven D. Buckingham , David B. Sattelle , Susan Wonnacott , Adrian J. Wolstenholme1,4,5* 1 Departmenty of Biology and Biochemistry, University of Bath, Bath, United Kingdom, 2 Wadham College, University of Oxford, Oxford, United Kingdom, 3 Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom, 4 Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America, 5 Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America Abstract Anthelmintic resistance is a major problem in livestock farming, especially of small ruminants, but our understanding of it has been limited by the difficulty in carrying out functional genetic studies on parasitic nematodes. An important nematode infecting sheep and goats is Haemonchus contortus; in many parts of the world this species is resistant to almost all the currently available drugs, including ivermectin. It is extremely polymorphic and to date it has proved impossible to relate any sequence polymorphisms to its ivermectin resistance status. Expression of candidate drug-resistance genes in Caenorhabditis elegans could provide a convenient means to study the effects of polymorphisms found in resistant parasites, but may be complicated by differences between the gene families of target and model organisms. We tested this using the glutamate-gated chloride channel (GluCl) gene family, which forms the ivermectin drug target and are candidate resistance genes. We expressed GluCl subunits fr