Parasitic nematode infections are common in both humans and livestock populations around the globe. In humans, these infections cause illness which can be debilitating. In livestock, parasitic nematode infections result in poor animal health and wellbeing as well as decreases in the yield of these animals. The decrease in yield from animals causes billions in lost revenue each year. In order to combat these parasitic nematode infections we use anti-helminth or anthelmintic drugs. These anthelmintic drugs come in a couple major classes including: benzimidazoles, macrocyclic lactones, nicotinic acetylcholine receptor agonists, and amino-acetonitrile derivatives and other smaller classes with few drugs. Unfortunately, resistance to anthelmintic drugs is extremely common and continuing to appear globally. Resistance to benzimidazoles has been observed since the 1960s. Because benzimidazoles were the first anthelmintic class developed and one of the first to have documented resistance, large amounts of research have been conducted on the mechanisms of resistance. This research has led to the discovery of ben-1 as the target of benzimidazoles in Caenorhabditis elegans. Additionally, orthologs of ben-1 in parasitic nematodes have been discovered to have alleles that are correlated with resistance. Unfortunately, because of the difficulty in culturing parasites these alleles have not been tested or validated. In this thesis, I have validated that all currently identified putative resistance alleles confer resistance to benzimidazoles. In addition to validating the ability to confer resistance, I have measured the fitness of nematodes with each of the resistance alleles compared to wild type to identify potential fitness consequences associated with these alleles. I have identified one allele that causes individuals to be less fit than wild-type. Additionally, I have tested five alleles to determine if the resistance phenotypes they confer are dominant or recessive and found that all of these alleles confer recessive resistance phenotypes. Beyond the ben-1 locus, I have identified a locus in C. elegans that modifies response to the benzimidazole thiabendazole. The identified locus, cyp-35D1, has three naturally occurring alleles that modify response to thiabendazole. Overall, this thesis has aimed to test hypotheses generated in parasites in C. elegans and to generate new hypotheses that need to be researched in parasitic nematodes.

Creator

• Dilks, Clayton Matthew

DOI

• https://doi.org/10.21985/n2-rv1t-fr03

Subject

• Molecular biology
• Genetics

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:15713
• etdadmin_upload_843341

Keyword

• Parasites
• Anthelmintics
• beta-tubulin
• C. elegans

Date created

• 2021-01-01

Resource type

• Dissertation

Rights statement

• In Copyright