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

Elife. 2023 Jun 9:12:e76584. doi: 10.7554/eLife.76584.


Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically defined diets, we found that association with Lp improves the growth of larvae-fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its host's growth through a molecular dialogue that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the general control nonderepressible 2 (GCN2) kinase in Drosophila's enterocytes. Our data indicate that Lp's r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialogue between host and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.

Keywords: D. melanogaster; GCN2; Lactobacillus; developmental biology; infectious disease; microbiology; symbiosis.

MeSH terms

  • Amino Acids
  • Animals
  • Cues
  • Drosophila
  • Drosophila Proteins* / genetics
  • Larva / genetics
  • Operon
  • Protein Kinases
  • RNA, Transfer
  • Symbiosis*


  • RNA, Transfer
  • Amino Acids
  • GCN2 protein, Drosophila
  • Protein Kinases
  • Drosophila Proteins

Associated data

  • SRA/PRJNA799161