Bacterial purine metabolism modulatesC. elegansdevelopment and stress tolerance via DAF-16 translocation

Abstract

AbstractPurine 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 utilizedCaenorhabditis elegansas the metazoan model. Through a high-throughput screening of anE. colimutant library Keio collection, we identified 34E. colimutants that delayC. elegansdevelopment. Among these mutants, we found thatE. coli purEgene 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 fedE. 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 theE. coli purEmutant 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 nematodeC. elegansthrough DAF-16 nuclear translocation.