ABC-transporter gene expression in ivermectin-susceptible and resistant Haemonchus contortus isolates

Vet Parasitol. 2022 Feb;302:109647. doi: 10.1016/j.vetpar.2022.109647. Epub 2022 Jan 7.

Abstract

Mammalian efflux transporters of the ATP-binding cassette (ABC) regulate cellular levels of endo- and xenobiotics by transporting molecules across cell membranes and are involved in diverse biological processes. Over-expression of these ABC transporters has been involved in macrocyclic lactone resistance. The main goal of this work was to compare the gene expression of the whole ABC-transporter superfamily in isolates of the sheep nematode Haemonchus contortus with different degrees of susceptibility to ivermectin (IVM). Additionally, the effects of in vivo IVM treatment were evaluated in the resistant isolates. Parasite-free Corriedale lambs were artificially infected with either IVM-susceptible or IVM-resistant H. contortus isolates. The differential expression of ABC transcripts in H. contortus female worms with differential susceptibility to IVM were assessed by RNA-seq. Additionally, the transcription levels of ABC-transporter genes in IVM-resistant adult worms recovered from treated sheep at 12 and 24 h after IVM administration were compared to those of IVM-R worms collected from untreated sheep. The comparative analysis of the ABC-transcripts revealed some minor differences in the expression levels of HCON_00042800 (pgp-3), HCON_00020200.mod (ced-7c), HCON_00085890 (abt-4), HCON_00063000 (pmp-5) and HCON_00116670 (wht-8), indicating that, at transcriptional level, these ABC-genes alone cannot explain resistance in H. contortus. HCON_00130060 (pgp-9.2) was highly differentially expressed in resistant isolates compared to susceptible ones, which agrees with previous reports suggesting that pgp-9 may be one of the most relevant candidates contributing to the multi-genic nature of the IVM resistance trait.

Keywords: ABC-transporters; Drug resistance; Haemonchus contortus; Ivermectin; Transcriptomic profiling.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Anthelmintics* / pharmacology
  • Drug Resistance / genetics
  • Female
  • Gene Expression
  • Haemonchiasis* / drug therapy
  • Haemonchiasis* / veterinary
  • Haemonchus* / genetics
  • Ivermectin / pharmacology
  • Ivermectin / therapeutic use
  • Sheep
  • Sheep Diseases* / drug therapy

Substances

  • ATP-Binding Cassette Transporters
  • Anthelmintics
  • Ivermectin