Are Post-Transcriptional RNA Modification Events in the Glutamate-Gated and GABA-Gated Chloride Channels of Anopheles minimus and Anopheles dirus associated with Ivermectin Insensitivity?

Mosquito-borne diseases, most notably malaria, have been a constant public health challenge in many regions around the world claiming the lives of hundreds of thousands every year. Vector control strategies such as insecticide use were initially effective in reducing malaria transmission. However, the emergence and ever-increasing presence of insecticide resistance has drastically hindered malaria control efforts. Insecticide resistance develops through various mechanisms, one of which involves changes to the insecticide’s target site. Recent studies have highlighted the effective use of the drug ivermectin (IVM) as a malaria vector control tool, which kill mosquitoes by having a detrimental effect on neuronal functions by acting on the glutamate-gated (GluCl) and the GABA-gated (RDL) chloride channels. The mechanism by which this is achieved is poorly understood. Using a combination of molecular and bioinformatic techniques such as DNA/RNA extraction, PCR amplification and DNA/RNA sequence analysis of the GluCl and RDL channels, this study aimed to elucidate any differences in DNA and RNA sequences in the mosquito species Anopheles minimus and Anopheles dirus and their possible association with IVM sensitivity as these species display differential sensitivities to IVM. The results obtained from this study have identified polymorphisms, several cases of RNA A-to-I editing, and alternative splicing of the An. minimus and An. dirus GluCl and RDL channels. Potentially novel RNA editing sites and splice variants have also been identified. While these results provide promising routes for further research, the limited sample size of this study makes further testing necessary to validate these findings.

Grantor dc:publisher

Oxford Brookes University

Author dc:creator

• Hotwagner, David

Contributors dc:contributor

• Jones, Andrew K.

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/x9zd-qh38

OAI identifier oai:identifier

tle:13bbb3d5-5be7-49d0-a1e8-91f828b2e2e7:d6bd9758-527a-46cd-bfe2-c433766e8fca:1