Identification of bacterial signals that modulate enteric sensory neurons to influence behavior in C. elegans

The bacterial microbiome influences many aspects of animal health and disease. Bacteria can have beneficial functions, for example providing nutrients, whereas others can act as pathogens. Bacteria are sensed by host cells to induce adaptive changes in physiology and behavior. While immune and intestinal cells detect bacterial signals through well-characterized mechanisms, recent studies indicate that neurons can also directly sense bacteria. However, the bacterial sensory mechanisms in neurons are less well understood. In Caenorhabditis elegans, the enteric sensory neuron NSM innervates the pharyngeal lumen and is directly activated by bacterial ingestion; in turn, NSM releases serotonin to induce feeding-related behaviors. However, the molecular identities of the bacterial signals that activate NSM are unknown. To identify them, we probed bacterial macromolecules from nutritive bacteria using biochemical approaches. We find that polysaccharides from bacteria are sufficient to activate NSM. We further identify peptidoglycans from Gram-positive bacteria as specific components capable of activating NSM. NSM responses to polysaccharides require the acid-sensing ion channels DEL-3 and DEL-7, which localize to NSM's sensory dendrite in the pharyngeal lumen. Ingestion of bacterial polysaccharides enhances feeding and reduces locomotion, matching the known effects of NSM on behavior. We also examine signals produced by pathogenic bacteria. This approach identifies prodigiosin, from pathogenic Serratia marcescens, as a metabolite that prevents NSM activation by nutritive bacterial signals. This study identifies molecular signals that underlie neuronal recognition of nutritive bacteria in the alimentary canal and competing signals from a pathogenic bacterial strain that can mask this form of recognition.