bioRxiv · Sep 18, 2023
Bacterial purine metabolism modulates C. elegans development and stress tolerance via DAF-16 translocation
By Feng M, Gao B, Garcia LR et al.
Abstract Purine homeostasis is crucial for cellular function and is a conserved metabolic network from prokaryotes to humans. While extensively studied in microorganisms like yeast and bacteria, the impact of perturbed dietary purine levels on animal development and balanced growth remains poorly understood. To investigate the mechanisms underlying this deficiency, we utilized Caenorhabditis elegans as the metazoan model. Through a high-throughput screening of an E. coli mutant library Keio collection, we identified 34 E. coli mutants that delay C. elegans development. Among these mutants, we found that E. coli purE gene is an essential genetic component that promotes host development in a dose-dependent manner. Additionally, we observed increased nuclear accumulation of the FoxO transcription factor DAF-16 when fed E. coli purE- mutants, suggesting the role of DAF-16 in response to nutrient, especially purine deficiency. RNA-seq analysis and phenotype assays revealed that worms fed the E. coli purE mutant exhibited elevated lifespan, thermotolerance, and pathogen resistance. These findings collectively suggest that perturbations in bacterial purine metabolism likely serve as a cue to promote development and activate the defense response in the nematode C. elegans through DAF-16 nuclear translocation.