Studying Xenorhabdus Genomes for Insight into Neurochemical Animal-Microbe Interactions

Nematodes are effective models for understanding molecular bases of animal-microbe interactions, including how bacterial products impact animal development and behavior. Steinernema nematodes coordinate specific symbioses with Xenorhabdus bacteria. The bacteria provide a food source and virulence factors when infecting insects. In turn, the nematodes transport bacteria between hosts. Previous preliminary data implicated the Xenorhabdus nematophila enzyme HpaBC in modulating Steinernema carpocapsae nematode egg-laying behavior. HpaBC’s role in organizing development and behavior was investigated using another nematode-bacterial pair, X. griffiniae and S. hermaphroditum, where an X. griffiniae strain was engineered with hpaBC under an inducible system. Modifying hpaBC expression significantly altered host growth and influenced egg-laying behavior in a similar manner to S. carpocapsae. Alongside HpaBC, numerous bacterial proteins likely mediate host developmental and behavioral impacts by interacting with neurotransmitter metabolic pathways. Two such enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MOAA), are critical in metabolizing neurotransmitters like dopamine and serotonin. Computational analysis revealed homologs of both enzymes encoded within select Xenorhabdus strains, with the distribution of COMT and MOAA loci forming distinct clusters within the genus. Given the similarity of these enzymes to human homologs targeted by antidepressants, understanding how bacteria modulate host physiology could provide insights into numerous microbiota-related disorders.