Uracil-Driven ROS signals activate larval TrpA1-B neurons to prime the Drosophila adult gustatory response to bacterial signal

Abstract

Animals perceive their environment through their sensory systems why rely on neuronal circuits and proteins, but can be modulated by internal physiological conditions or exogenous factors. We have 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. We identify here uracil as the bacterial metabolite responsible for this priming and demonstrate that the effect is mediated by Duox-dependent production of reactive oxygen species in the larval gut. We 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 Duox/ROS and TrpA1/Gr66a modules as key mediators linking larval gut microbial signals and host integration to subsequent sensory system modulation in the adult. HighlightsO_LIBacterial uracil primes larvae to drive adult aversion to peptidoglycan C_LIO_LIDuox-dependent ROS in larval enterocytes are required for sensory priming C_LIO_LITrpA1 B/C/E isoforms in a larval Gr66a+ neuron mediate priming C_LIO_LIUracil induces Duox/ROS signals enabling inter-larval activation of TrpA1-B+ neurons C_LI