Emergence and the spread of the F200Y benzimidazole resistance mutation in Haemonchus contortus and Haemonchus placei from buffalo and cattle

Abstract

9Benzimidazoles have been intensively used in the livestock sector, particularly in small 3 0 ruminants for over 40 years. This has been led to the widespread emergence of resistance in a 3 1 number of small ruminant parasite species, in particular Haemonchus contortus. In many 3 2 counties benzimidazole resistance in the small ruminants H. contortus has become severely 3 3 compromising its control; but there is a little information on benzimidazole resistance in H. 3 4 contortus infecting buffalo and cattle. Resistance to benzimidazoles have also been reported 3 5 in the large ruminant parasite, Haemonchus placei, but again there is relatively little 3 6 information on its prevalence. Hence it is extremely important to understand how resistance-3 7 conferring mutations emerge and spread in both parasites in the buffalo and cattle host in 3 8 order to develop the approaches for the recognition of the problem at an early stage of its 3 9 development. The present study suggests that the F200Y (TAC) mutation is common in H. 4 0 contortus, being detected in 5/7 populations at frequencies between 7 to 57%. Furthermore, 4 1 6/10 H. placei populations contained the F200Y (TAC) mutation, albeit at low frequencies of 4 2 between 0.4 to 5%. The phylogenetic analysis suggests that the F200Y (TAC) mutation in H. 4 3 contortus has emerged on multiple occasions in the region, with at least three independent 4 4 emergence of resistance alleles across the populations. In contrast, the F200Y (TAC) 4 5 resistance-conferring mutation in H. placei is only seen on a single haplotype. A high level of 4 6 haplotype frequency of the susceptible alleles in the region, suggests that the unique 4 7 resistance conferring-mutation has spread from a single emergence; likely by anthropogenic 4 8 animal movement. Overall, these results provide the first clear genetic evidence for the 4 9Recently, we have developed and validated the Illumina Mi-seq deep amplicon sequencing

Evidence for the F200Y (TAC) mutation conferring benzimidazole resistance in a southern USA cattle population of Haemonchus placei spreading from a single emergence

“…First, benzimidazole resistance could emerge as a new mutation and then spread through populations by host migration, likely as a consequence of animal movements: in this case a single resistance haplotype is present in each population. This has been observed for the benzimidazole resistance conferring allele E198A (G C A) in H. contortus (Chaudhry et al, 2015d) and more recently F200Y (T A C) in H. placei (Ali et al, 2019b). Second, benzimidazole resistance could repeatedly emerge multiple time by recurrent or pre-existing mutations and migrate between nematode parasite populations as a result of host movement.…”

“…We have detected the F200Y (T A C) mutation in 6 out of 9 H. placei populations. These results suggest that the F200Y (T A C) resistance mutation is likely to be present in many H. placei populations in southern US cattle, observed by Brasil et al (2012) and Ali et al (2019b). The presence of this mutation at a low frequency would not be expected to result in detectable loss of efficacy of benzimidazole drug (Ali et al, 2019a).…”

“…These results suggest that the F200Y (T A C) resistance mutation is likely to be present in many H. placei populations in southern US cattle, observed by Brasil et al (2012) and Ali et al (2019b). The presence of this mutation at a low frequency would not be expected to result in detectable loss of efficacy of benzimidazole drug (Ali et al, 2019a). In the present study, phylogenetic analysis of H. placei F200Y (T A C) resistance haplotype (Hr3) supports the hypothesis that it emerged from a single resistance mutation.…”

“…This has led to the development of resistance in a number of small ruminant parasite species including H. contortus (Chaudhry, 2015). Benzimidazole resistance has been reported in closely related cattle parasite H. placei , but there is relatively little information on its prevalence (Ali et al, 2019a; Brasil et al, 2012). In the present study, we proposed that benzimidazole conferring resistance would be at early stage of development in H. placei as compared to H. contortus in southern USA due to less drug selection pressure in cattle as compared to small ruminants.…”

“…Nonetheless, benzimidazole resistance is now emerging and represents a serious challenge to the cattle industry worldwide (Sutherland and Leathwick, 2011). There have been relatively few studies of the genetic determinants of benzimidazole resistance in H. placei (Ali et al, 2019a; Brasil et al, 2012).…”