Intestinal GCN2 controls Drosophila systemic growth upon AA imbalance in response to Lactiplantibacillus plantarum symbiotic cues encoded by r/tRNA operons

Abstract Symbiotic bacteria support host growth upon malnutrition. How bacteria achieve this remains partly elusive. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate such mechanisms. Using chemically-defined holidic diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets. We show that in this context Lp supports its host’s growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophila’s enterocytes. Our data indicate that Lp’s r/tRNAs loci products activate GCN2 in a subset of larval enterocytes, a mechanism necessary for the host’s adaptation to amino acid imbalance that ultimately supports growth. Our findings unravel a novel beneficial molecular dialog between hosts and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons