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

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.