Multisensory pathogen detection drives rapid escape and shapes host-microbe interactions in Drosophila larvae.

Larvae of many insects develop immersed in decomposing substrates densely populated with microbes, yet how they detect and respond to pathogenic threats during early life remains poorly understood. Here, we show that Drosophila melanogaster larvae exhibit a previously unrecognized rapid escape behavior triggered by food contaminated with metabolically active Erwinia carotovora carotovora 15 (Ecc15), a natural bacterial pathogen of flies and plants. Stationary-phase cells fail to elicit avoidance, demonstrating that larval detection of Ecc15 depends on bacterial metabolic activity rather than on its mere presence. Using targeted genetic manipulations, we identify two chemosensory pathways required for this response: a gustatory input mediated by the aversion receptor Gr33a and an olfactory input involving the Or49a-Orco complex. Disrupting either pathway abolishes escape, revealing that larvae rely on coordinated gustatory and olfactory signals to evaluate and respond to microbial dangers. Functionally, escape limits contact time with contaminated substrates and enables larvae to reach uncontaminated food, partially mitigating the developmental impact of early pathogen exposure. However, dispersing larvae also transfer viable bacteria to new substrates, indicating that this avoidance behavior concurrently promotes pathogen spread. Together, these findings establish the first example of a rapid, multisensory escape behavior induced by a natural pathogen in Drosophila larvae and provide a tractable model for dissecting how microbial cues guide behavioral decision-making and influence pathogen dissemination.