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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 Escherichia coli alters sensory-driven behaviors in both larval and adult axenic Drosophila melanogaster. In larvae, E. coli 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, E. coli mono-association increased attraction to fermentation cues (apple cider vinegar, ethanol) and enhanced sucrose consumption in wild-type and Orco-deficient flies, whereas these effects were reduced or absent in IR co-receptor mutants (IR25a\u2212 and IR76b\u2212). Together, these findings indicate that under defined gnotobiotic conditions, E. coli 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.<\/jats:p>","DOI":"10.3390\/insects17030275","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:18:45Z","timestamp":1772554725000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Escherichia coli Mono-Association Modulates Ionotropic Receptor-Dependent Behaviors in Drosophila melanogaster"],"prefix":"10.3390","volume":"17","author":[{"given":"Hazem","family":"Al Darwish","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Cacao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deep","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sammi","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safiyah","family":"Salama","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muqaddasa","family":"Tariq","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8688-1103","authenticated-orcid":false,"given":"Aina T.","family":"Ananda","sequence":"additional","affiliation":[{"name":"Department of Biology, Monmouth University, 400 Cedar Avenue, West Long Branch, NJ 07764, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4274-0504","authenticated-orcid":false,"given":"Jennifer S.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Depetris-Chauvin, A., Galagovsky, D., and Grosjean, Y. 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