SUMMARYBenzimidazoles resistance in Teladorsagia circumcincta, a nematode parasite of small ruminant. Studies of genetic determinism and research for parasite fitness consequences.
Resistance to benzimidazols (BZs) in Teladorsagia circumcincta, a common nematode parasite of small ruminants, can become a major problem for sheep and goat farmers if no control measure is taken to limit its development. The objectives of the study were to assess the genetic mechanisms which permit the nematode to become resistant and, on the other hand, to survey this phenomenon at the population level.
We have demonstrated that BZs resistance in T. circumcincta is mainly due to a mutation on the anthelmintic target gene, the b -tubulin gene. This mutation is at the origin of the replacement of a Phenylalanin by a Tyrosin at the position 200 of the protein. It is a recessive mutation as only homozygous resistant individuals stayed alive after treatments and seemed present in the majority of natural populations. The proportion of homozygous resistant individuals in natural populations is positively correlated to the LD50 level of resistance.
We have also demonstrated that the fitness of the three genotypes (rr, rS and SS) was similar in experimental conditions. First results in natural conditions confirmed this results, as field observations which never demonstrated a reversion of resistance. Concerning the origin of mutant allels, we demonstrated that this mutation could be located on different allels of b -tubulin gene, indicating that resistance could independantly appear in different farms. Inversely, a number of populations had similar mutant allels, indicating they existed before the creation of the flock or were introduced by migratory processes. Resistant populations of worms presented a low b -tubulin gene polymorphism which seemed due to an auto-stop effect generated by the invasion of the benefical mutation in the population with a number of other proximal and neutral mutations.
Numerous prospects could be identified after this work in order to complete knowledge on the genetical determinism of BZs resistance in this nematode species when high levels of resistance to these coumpounds are observed. Between population surveys will be running to compare the fitness of the genotypes and to analyse the origin of the mutant allels. Other applied protocols are initiated to try to control resistance by limiting mutant selection and by identifying management factors which are favourable for selecting resistant individuals.