Myers, T. G.; Goodrich-Blair, H.; Heppert, J.

Beneficial animal-microbe symbioses occur across the tree of life, with observable impacts on animal development and behavior. Some of these impacts occur when microbial enzymes act upon host-derived metabolites. The bacterial enzyme complex HpaBC hydroxylates aromatic compounds, including tyrosine and precursors of the neurotransmitter dopamine, raising the possibility that this enzyme may indirectly impact neurotransmitter-dependent phenotypes. The bacterium Xenorhabdus griffiniae, a beneficial intestinal symbiont of Steinernema hermaphroditum entomopathogenic nematodes, encodes HpaBC. Computational docking of X. griffiniae HpaB affinity for dopamine pathway substrates revealed energetically favorable docking of both dopamine and tyrosine, though neither was as favorable as the predicted affinity of HpaB for the canonical substrate, 4-hydroxyphenylacetate. We hypothesized that Xenorhabdus HpaBC may influence nematode host development or behavior through its potential action on tyrosine degradation or dopamine catabolism. In support of this idea, we demonstrate a negative correlation between X. griffiniae hpaBC expression and body length and egg-laying behavior in adult S. hermaphroditum nematodes. Moreover, hpaBC expression is necessary for X. griffiniae bacteria to colonize the nematode intestine in the infective juvenile stage. Taken together, these findings indicate that HpaBC may be a part of the metabolic crosstalk occurring between X. griffiniae and S. hermaphroditum at multiple stages of their shared life cycle. hpaBC orthologs are widely present across bacterial phyla including in pathogens and mutualists of plants and animals. Our findings raise the possibility that HpaBC could be a conserved mechanism by which host-associated bacteria influence physiology and behavior.