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Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells

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Intestinal GCN2 controls Drosophila systemic growth in response to Lactiplantibacillus plantarum symbiotic cues

Théodore Grenier¹, Jessika Consuegra¹, Mariana G Ferrarini^2,3

¹Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Superieure de Lyon, Université Claude Bernard, Lyon, France.

|June 9, 2023

Summary

This summary is machine-generated.

Symbiotic bacteria Lactiplantibacillus plantarum (Lp) enhance Drosophila larval growth on imbalanced diets. Lp uses extracellular vesicles containing ribosomal/transfer RNAs (r/tRNAs) to activate host GCN2 kinase, promoting anabolic growth.

Keywords:

D. melanogaster GCN2 Lactobacillus developmental biology infectious disease microbiology symbiosis

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Area of Science:

Microbiology
Genetics
Developmental Biology

Background:

Host-microbe interactions are crucial for organismal development and health.
Symbiotic bacteria communicate with hosts via specific molecular cues.
The mutualism between Drosophila and Lactiplantibacillus plantarum offers a model to study host-symbiont dialogues.

Purpose of the Study:

To investigate a novel mechanism of host-symbiont interaction in Drosophila.
To understand how Lactiplantibacillus plantarum (Lp) supports host growth on nutrient-limited diets.
To elucidate the role of ribosomal and transfer RNAs (r/tRNAs) in mediating symbiotic communication.

Main Methods:

Utilized chemically defined diets to control nutrient availability for Drosophila larvae.
Investigated the function of Lp's ribosomal and transfer RNA (r/tRNA) operons.
Examined the role of Drosophila's general control nonderepressible 2 (GCN2) kinase in enterocytes.
Analyzed the packaging of Lp's r/tRNAs in extracellular vesicles.

Main Results:

Lp association improved Drosophila larval growth on amino acid-imbalanced diets, despite Lp not producing the limiting amino acid.
Lp's r/tRNAs, packaged in extracellular vesicles, were found to activate GCN2 kinase in larval enterocytes.
Activation of GCN2 by Lp's r/tRNAs remodeled the intestinal transcriptome, supporting anabolic growth.
Functional r/tRNA operons in Lp and GCN2 in host enterocytes were essential for this growth-promoting interaction.

Conclusions:

Proposed a novel beneficial molecular dialogue between Drosophila and Lactiplantibacillus plantarum.
Demonstrated a non-canonical role for GCN2 kinase in mediating symbiotic cues.
Highlighted the importance of microbial extracellular vesicles carrying r/tRNAs in host-microbe communication and host physiology.