Effect of selection for benzimidazole resistance in Haemonchus contortus on beta-tubulin isotype 1 and isotype 2 genes.
In vitro selection for benzimidazole (BZ) resistance in the nematode Haemonchus contortus, a parasite of sheep, suggested the involvement of beta-tubilin genes. Two distinct beta-tubulin isotype classes were analyzed. Selection with stepwise increased concentrations of BZ showed for the first time that the increasing degrees of resistance correlate to a dual phase adaptation mechanism. At lower degrees of developing resistance, selection for a single beta-tubulin isotype 1 variant takes place. Subsequently, at higher degrees of drug resistance, an abrupt elimination of individuals carrying beta-tubulin isotype 2 genes in their genome is seen. To evaluate the in vitro experiments we carried out a survey of resistant field populations and found that in the most resistant population (RNO) apparently the same mechanism had happened.
Kwa
M S
MS
Department of Parasitology and Tropical Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Kooyman
F N
FN
Boersema
J H
JH
Roos
M H
MH
D000818:Animals; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology*; D004277:DNA, Single-Stranded; D004351:Drug Resistance; D006189:Haemonchus / Q000187:drug effects*; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D014404:Tubulin / Q000235:genetics*
D001562:Benzimidazoles; D004277:DNA, Single-Stranded; D014404:Tubulin; C031000:benzimidazole