Your Mind’s Microbe: Investigating Bacterial-Derived HpaB as a Regulator of Gut-Brain Interactions

Host-microbe interactions routinely shape animal physiology, particularly within the gut microbiome, where microbial metabolites can influence neurological development and function through the gut-brain axis, including through the production of neurotransmitter-like molecules. In this context, Xenorhabdus species, bacterial symbionts of Steinernema nematodes, provide compelling models for these interactions due to their genetic tractability and intricate metabolic networks. Prior investigations in this model system revealed that expression of hpaB, which encodes the oxygenase component of the 4-hydroxyphenylacetate-3-monooxygenase (HpaBC) in X. griffiniae, to impact developmental and behavioral patterns in its host nematode, S. hermaphroditum. Seeking to understand HpaBC in its ability to bind neurotransmitter-like molecules and action across Xenorhabdus and related bacterial taxa, tools like SwissDock, Phyre2, and AlphaFold were employed. Structural analyses indicate that HpaB is a cytoplasmic, globular protein with a hydrophilic exterior. Docking simulations suggest that, while 4-hydroxyphenylacetate remains the preferred substrate, similar molecules like dopamine and its metabolite, DOPAC, exhibit significant binding affinity, supporting a potential role in neurotransmitter metabolism. While computational data suggest HpaBC’s substrate versatility, future work is required to experimentally validate these interactions and their implications in host-microbe interactions. This research bolsters a broader understanding of bacterial metabolic pathways and their role in modulating host physiology.