Towards Characterization of a Nematode Stress Reporter Suppressing Streptomyces Extract for Anthelmintic Use
Year: 2019
Type: dissertation
Abstract: Parasitic worms, commonly termed helminths, infect >20% of humans, livestock, and agricultural crops worldwide. Helminths exhibiting resistance to most anthelmintic classes are emerging and new drugs are needed to lessen the burden on the global economy and public health. Here, I probed a library of potentially novel natural products (NPs) towards identifying bioactive compounds against stress response pathways in helminths using the model nematode Caenorhabditis elegans. NPs account for >50% of FDA-approved therapeutics, with the bacterial genus Streptomyces producing >50% of the most important microbial NPs. In total, I screened 970 Streptomyces extracts and found 82 that suppressed stress response reporters in C. elegans. I focused on one extract that suppressed the infection stress reporter NLP-29. Unfortunately, this bioactivity was challenging to reproduce. I present my screening, biochemical purification, and target characterization efforts, emphasize implemented controls along the project pipeline, and propose additional measures for a more stringent future pipeline.
Source: TSpace (University of Toronto)
Author: Yeonwha Song
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3158723522