Dr. Jacqueline Hellinga (Berlin / DE), Barbora Trubenova (Zürich / CH), Jessica Wagner (Berlin / DE), Agnes Piecyk (Kiel / DE), Roland Regoes (Zürich / CH), Hinrich Schulenburg (Kiel / DE), Dr. Jürgen Krücken (Berlin / DE), Prof. Dr. Georg von Samson-Himmelstjerna (Berlin / DE)
Abstract text
Introduction:
Free-living nematodes such as Caenorhabditis elegans (C. elegans) are an appealing tool for experimental evolution, given the easiness of working with them in cultured laboratory conditions. C. elegans is also a critical model for parasitic nematodes working with antiparasitic drugs, from understanding current and new drugs' molecular mechanisms to uncovering more drug targets. This is critical to counter the increase in antiparasitic drug resistance. However, the research of antiparasitic drugs with C. elegans has not been investigated from an evolutionary aspect.
Objective:
We present an evolution experiment detailing the impact of intrinsic factors such as population size and genetic diversity on the rate of ivermectin resistance evolution.
Methods:
We used a step-wise ivermectin introduction experiment to evolve resistant strains, which a mathematical model accompanied. The starting ancestor and final ivermectin-resistant populations were subjected to transcriptomic analysis by RNASeq and larval development assays with various anthelmintics.
Results:
We found that having a genetically diverse population shortened the time it took for the worms to evolve resistance to ivermectin. Different population sizes directly correlated to the rate of ivermectin resistance during the evolutionary experiment. This correlation was also predicted by mathematical modeling. Our RNASeq analysis is ongoing, yet we have many differences in gene expression between the ancestor and resistant worm populations. Lastly, our ivermectin-resistant populations were still sensitive to monepantel and albendazole but resistant to moxidectin and unexpectedly also to emodepside.
Conclusion:
The work done here is the first of many examples using evolution experiment guidelines to find answers for understanding which factors could influence the occurrence of anthelmintic resistance. We found that intrinsic factors such as genetic diversity and population size play a definitive role in the rate of ivermectin resistance formation in our evolutionary experiment. Our post-evolutionary experiments found that our ivermectin-resistant populations are also resistant to other macrocyclic lactones yet sensitive to other classes of anthelmintic drugs.