Identification of variant ABC-transporter genes among Onchocerca volvulus collected from ivermectin-treated and untreated patients in Ghana, West Africa.
Treatment with ivermectin (IVM) is known to cause a loss of polymorphism at certain loci of the beta-tubulin, gamma-aminobutyric-acid-receptor, glutamate-gated-chloride-channel and ATP-binding-cassette (ABC) transporter genes of IVM-resistant Haemonchus contortus. The genetic variation of four ABC-transporter homologues from Onchocerca volvulus was therefore investigated, to determine if any change in genetic polymorphism occurs in these genes following repeated treatment with IVM. Samples were collected in the Northern, Brong-Ahafo and Volta regions of Ghana, in 1999 and 2002; nodules containing adult O. volvulus were removed from subjects who had either received multiple IVM treatments or never taken IVM. The ATP-binding domains of four ABC-transporter genes (OvMDR-1, OvMDR-3, OvABC-1 and OvABC-6) were amplified from individual O. volvulus and examined for polymorphism, using single-strand-conformation-polymorphism (SSCP) analysis. In the samples collected in 1999, OvMDR-1 and OvABC-1 showed significant reduction in polymorphism following IVM treatment whereas OvABC-6 and OvMDR-3 were not found to be polymorphic. The samples collected in 2002 also showed a reduction in polymorphism for both OvMDR-1 and OvABC-1. Several single-nucleotide polymorphisms, which resulted in either amino-acid-replacement substitutions or nonsense mutations, were identified in the alleles of OvMDR-1 and OvABC-1.
Ardelli
B F
BF
Institute of Parasitology, McGill University, 21-111 Lakeshore Road, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada.
Prichard
R K
RK
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D003001:Cloning, Molecular; D005369:Filaricides / Q000627:therapeutic use*; D017125:Genes, Protozoan / Q000235:genetics*; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use*; D017181:Onchocerca volvulus / Q000187:drug effects / Q000235:genetics*; D009855:Onchocerciasis / Q000188:drug therapy* / Q000453:epidemiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D016415:Sequence Alignment
D018528:ATP-Binding Cassette Transporters; D005369:Filaricides; D007559:Ivermectin