Intestinal GCN2 controls Drosophila systemic growth in response toLactiplantibacillus plantarumsymbiotic 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.

Structure–function analysis of Lactiplantibacillus plantarum DltE reveals D-alanylated lipoteichoic acids as direct cues supporting Drosophila juvenile growth

“…Similarly to PG fragments, which are shaded in the extracellular media during bacterial cell division, LTA chains may also be shed after cleavage of the lipid anchor ( Neuhaus and Baddiley, 2003 ). In addition, our recent findings report Lp NC8 ’s ability to release microvesicles of multi-nanometers ranges ( Grenier et al, 2021 ). This observation is coupled to previous reports showing that other Lactobacillus strains form microvesicles containing LTAs that are endocytosed by mammalian enterocytes ( Champagne-Jorgensen et al, 2021 ), it is tempting to speculate that Lp NC8 D-Ala-LTAs are released via bacterial microvesicles cargo.…”

Structure-Function analysis of Lactiplantibacillus plantarum DltE reveals D-alanylated lipoteichoic acids as direct symbiotic cues supporting Drosophila juvenile growth

“…Similarly to PG fragments, which are shaded in the extracellular media during bacterial cell division, LTA chains may also be shaded after cleavage of the lipid anchor 36 . In addition, our recent findings report Lp NC8 's ability to release microvesicles of multi-nanometers ranges 37 Given the strong analogies of the impact of L. plantarum strains on Drosophila and Mouse growth 39 and previous work focusing on LTA in host-gram positive bacteria interactions 38,40 ,…”