Expression of nicotinic acetylcholine receptor subunits from parasitic nematodes in Caenorhabditis elegans

•The UNC-29 and UNC-38 of A. suum and H. contortus were expressed in C. elegans.•Hco-UNC-38 was able to rescue the lev and unc phenotypes of VC2397.•Asu-UNC-38 was not able to rescue these phenotypes.•Both UNC-29 proteins partially, but not fully, increased drug susceptibility.

The levamisole-sensitive nicotinic acetylcholine receptor present at nematode neuromuscular junctions is composed of multiple different subunits, with the exact composition varying between species. We tested the ability of two well-conserved nicotinic receptor subunits, UNC-38 and UNC-29, from Haemonchus contortus and Ascaris suum to rescue the levamisole-resistance and locomotion defects of Caenorhabditis elegans strains with null deletion mutations in the unc-38 and unc-29 genes. The parasite cDNAs were cloned downstream of the relevant C. elegans promoters and introduced into the mutant strains via biolistic transformation. The UNC-38 subunit of H. contortus was able to completely rescue both the locomotion defects and levamisole resistance of the null deletion mutant VC2937 (ok2896), but no C. elegans expressing the A. suum UNC-38 could be detected. The H. contortus UNC-29.1 subunit partially rescued the levamisole resistance of a C. elegans null mutation in unc-29 VC1944 (ok2450), but did cause increased motility in a thrashing assay. In contrast, only a single line of worms containing the A. suum UNC-29 subunit showed a partial rescue of levamisole resistance, with no effect on thrashing.

Graphical abstractSome nicotinic receptor subunits from parasitic species can be successfully expressed in C. elegans and rescue phenotypes associated with mutations in orthologous genes.Figure optionsDownload full-size imageDownload high-quality image (65 K)Download as PowerPoint slide