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Peer-reviewedCC BYPLOS Biology

Uracil-driven ROS signaling and larval TrpA1-B neuron activation are required for priming the adult Drosophila gustatory response to bacteria

  • Romane Milleville1
  • Gérard Manière2
  • Martine Berthelot-Grosjean2
  • Olivier Lamotte2
  • Yaël Grosjean2
  • Julien Royet1
  • Cyril Léopold Kurz1
  1. 1Aix-Marseille Université, CNRS, IBDM, Marseille, France.
  2. 2Université Bourgogne Europe, Institut Agro, CNRS, INRAE, UMR CSGA, Dijon, France.
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Abstract

Animals perceive their immediate environment through their sensory systems. While these systems rely on well-defined neuronal circuits and receptor proteins encoded by the genome, they can also be modulated by internal physiological conditions or exogenous factors. We have previously shown that the presence of certain pathogenic bacteria in the larval gut can alter the specificity of bacterial peptidoglycan recognition in the adults that emerge from these larvae. However, the nature of the bacterial signal and the host cells and molecules involved in receiving and transducing this signal remained unknown. Our results identify uracil as the bacterial metabolite responsible for this priming and demonstrate that the effect is mediated by Duox-dependent production of reactive oxygen species (ROS) in the larval gut. We further show that specific expression of TrpA1 isoforms in a Gr66a-expressing neuron of the larval terminal organ is required for the adult response. Together, these findings reveal uracil as the bacterial cue and the Duo/ROS signaling and TrpA1/Gr66a modules as key mediators linking larval gut microbial signals and host integration to subsequent sensory system modulation in the adult.

Pathogenic bacteria in the larval fly gut can ‘prime’ the adult gustatory system to recognize bacterial peptidoglycans, but how? This study identifies Uracil as the bacteria-derived cue and characterizes a larval sensory pathway required for priming the adult.

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Cite

BibTeXRIS
BibTeX
@article{milleville2026uracildriven,
  title = {{Uracil-driven ROS signaling and larval TrpA1-B neuron activation are required for priming the adult Drosophila gustatory response to bacteria}},
  author = {Romane Milleville and Gérard Manière and Martine Berthelot-Grosjean and Olivier Lamotte and Yaël Grosjean and Julien Royet and Cyril Léopold Kurz},
  journal = {PLOS Biology},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pbio.3004042},
  url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004042},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Uracil-driven ROS signaling and larval TrpA1-B neuron activation are required for priming the adult Drosophila gustatory response to bacteria
AU  - Romane Milleville
AU  - Gérard Manière
AU  - Martine Berthelot-Grosjean
AU  - Olivier Lamotte
AU  - Yaël Grosjean
AU  - Julien Royet
AU  - Cyril Léopold Kurz
PY  - 2026
DA  - 2026/10/05
JO  - PLOS Biology
DO  - 10.1371/journal.pbio.3004042
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004042
AB  - Animals perceive their immediate environment through their sensory systems. While these systems rely on well-defined neuronal circuits and receptor proteins encoded by the genome, they can also be modulated by internal physiological conditions or exogenous factors. We have previously shown that the presence of certain pathogenic bacteria in the larval gut can alter the specificity of bacterial peptidoglycan recognition in the adults that emerge from these larvae. However, the nature of the bacterial signal and the host cells and molecules involved in receiving and transducing this signal remained unknown. Our results identify uracil as the bacterial metabolite responsible for this priming and demonstrate that the effect is mediated by Duox-dependent production of reactive oxygen species (ROS) in the larval gut. We further show that specific expression of TrpA1 isoforms in a Gr66a-expressing neuron of the larval terminal organ is required for the adult response. Together, these findings reveal uracil as the bacterial cue and the Duo/ROS signaling and TrpA1/Gr66a modules as key mediators linking larval gut microbial signals and host integration to subsequent sensory system modulation in the adult.  Pathogenic bacteria in the larval fly gut can ‘prime’ the adult gustatory system to recognize bacterial peptidoglycans, but how? This study identifies Uracil as the bacteria-derived cue and characterizes a larval sensory pathway required for priming the adult.
SN  - 1545-7885
SN  - 1544-9173
ER  -