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The WormFood CURE: Screening for bioactive metabolites that antagonize the Caenorhabditis elegans Ras signaling
Emily Washeleski1, Emily Morrin1, Ryleigh Parsons1
1Department of Biological Sciences, Michigan Technological University, Houghton, MI, USA.
Abstract:
Course-based Undergraduate Research Experiences (CUREs) provide an accessible, scalable platform for scientific discovery. Here, we present the WormFood CURE, which mines environmental bacterial isolates for bioactive secondary metabolites using Caenorhabditis elegans phenotype suppression as a functional readout. Utilizing the multivulva (Muv) phenotype, our pilot cohort interrogated 41 wild bacterial isolates for suppression of Ras/MAPK signaling. We identified one Bacillus safensis isolate BAC-08 and one Bacillus altitudinis isolate BAC-44 that significantly inhibited ectopic vulval precursor cell (VPC) induction in Muv strains when fed as a live food source. BAC-08 and BAC-44 also significantly affected wild-type nematode development and growth. Metabolic pathway reconstruction from annotated genome assemblies did not support nutritional deficiency as the potential mechanism; instead, we observed that methanol-soluble intracellular extracts from BAC-44 were sufficient to inhibit pseudovulvae growth. We concluded that the observed Muv suppression is likely driven by a secondary metabolite effect. Comparative genomic analysis further identified unique biosynthetic gene clusters (BGCs) present in both BAC-08 and BAC-44 isolates compared to the other isolated Bacillus species. Altogether, our study demonstrates that the WormFood CURE model successfully identifies novel bacterial-genetic interactions, providing a scalable platform for discovery of new natural microbial products that modulate conserved eukaryotic signaling pathways.
Insights
The WormFood Course-based Undergraduate Research Experience (CURE) identified novel bacteria that suppress a key signaling pathway in nematodes. This scalable model discovers natural products modulating eukaryotic pathways.
Area of Science:
- Microbiology
- Genetics
- Biochemistry
Background:
- Course-based Undergraduate Research Experiences (CUREs) offer accessible platforms for scientific discovery.
- Mining environmental bacteria for bioactive compounds is crucial for natural product discovery.
Purpose of the Study:
- To present the WormFood CURE model for identifying bacterial secondary metabolites.
- To investigate bacterial isolates for their ability to modulate Caenorhabditis elegans signaling pathways.
Main Methods:
- Utilized the multivulva (Muv) phenotype in C. elegans to screen 41 bacterial isolates for Ras/MAPK signaling suppression.
- Fed live bacterial isolates and methanol-soluble extracts to nematodes.
- Performed metabolic pathway reconstruction and comparative genomic analysis.
Main Results:
- Identified Bacillus safensis BAC-08 and Bacillus altitudinis BAC-44 as suppressors of the Muv phenotype.
- Observed significant effects of BAC-08 and BAC-44 on wild-type nematode development and growth.
- Confirmed secondary metabolites, not nutritional deficiency, likely mediate the Muv suppression.
Conclusions:
- The WormFood CURE model successfully identifies novel bacterial-genetic interactions.
- This platform facilitates the discovery of natural microbial products that modulate conserved eukaryotic signaling pathways.
- Unique biosynthetic gene clusters were identified in the active bacterial isolates.
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