Satiety, TAX-4, and OSM-9 Tune the Attraction of C. elegans Nematodes to Microbial Fermentation Products

Animals are sensitive to selective pressures associated with nutrient acquisition, underscoring the evolutionary significance of chemosensation in foraging and its intersection with satiety. For the model nematode Caenorhabditis elegans, isoamyl alcohol (3-methyl-1-butanol) and 2-methyl-1-butanol are produced by microbial fermentation and present in bacterial food sources collected from the natural environments. Both compounds, which are structural isomers of one another, elicit strong attraction in laboratory settings. Using laboratory chemotaxis assays, we show that starvation attenuates attraction to both compounds. Well-fed C. elegans is largely insensitive to the biosynthetic precursors of both alcohols, with the exception of 4-methyl-2-oxovaleric acid, which is a mild repellent. C. elegans chemosensation relies on expression of tax-4 cyclic nucleotide-gated (CNG) and osm-9 transient receptor potential, vanilloid (TRPV) ion channels and animals lacking both genes are taste- and smell-blind. Animals lacking tax-4 fail to attract isoamyl alcohol and 2-methyl-1-butanol and those lacking osm-9 exhibit stronger attraction than the wild-type. Starvation not only attenuates attraction, but also enhances repulsion to 4-methyl-2-oxovaleric acid and uncovers repulsion in tax-4 mutants absent in their well-fed counterparts. Collectively, these findings implicate satiety in regulating response strength, tax-4-dependent chemotaxis in attraction to isoamyl alcohol and 2-methyl-1-butanol, and osm-9-dependent chemotaxis in suppressing responses to biosynthetic precursors.