Escherichia coli Mono-Association Modulates Ionotropic Receptor-Dependent Behaviors in Drosophila melanogaster

Chemosensory systems are crucial for insect survival, enabling host-seeking, food acquisition, and oviposition site selection. While insect-associated microbes are known to influence host development and immunity, their role in modulating chemosensory behavior remains poorly understood. Here, we show that mono-association with <i>Escherichia coli</i> alters sensory-driven behaviors in both larval and adult axenic <i>Drosophila melanogaster</i>. In larvae, <i>E. coli</i> mono-association altered phototaxis and mechanosensory responses across genotypes, while changes in tunneling and thermosensory behaviors were reduced or absent in ionotropic receptor (IR) co-receptor mutants. In adults, <i>E. coli</i> mono-association increased attraction to fermentation cues (apple cider vinegar, ethanol) and enhanced sucrose consumption in wild-type and <i>Orco</i>-deficient flies, whereas these effects were reduced or absent in IR co-receptor mutants (<i>IR25a</i>^- and <i>IR76b</i>^-). Together, these findings indicate that under defined gnotobiotic conditions, <i>E. coli</i> exposure alters sensory-driven behavioral outputs relative to axenic controls. Effects are reduced or absent in IR co-receptor mutants, consistent with a role for IR pathways in mediating these behavioral shifts. These findings support a role for microbial cues in shaping insect sensory-driven behaviors and highlight the importance of microbial status in interpreting behavioral phenotypes. This work provides a framework for future studies investigating how microbial signals interact with conserved sensory pathways.