Engineering commensal microbes to modulate neurohormonal balance
Abstract
Microbes sense and recognise host environment through diverse signalling mechanisms such as quorum sensing, a cell-to-cell signalling mechanism that responds to hormone-like chemical molecules called autoinducers (AIs), and activates cellular functionalities essential for colonization and virulence. Microbes recognize and respond to specific concentration thresholds of AIs, in turn altering genomic expression patterns. Notably, the bacterial chemical signal AI-3 can induce inter-kingdom signaling between prokaryotic and eukaryotic cells. This signal is also reported to cross-communicate with eukaryotic hormones epinephrine (epi) and norepinephrine (NE), both of which have important biological roles in the human GI, as well as direct effects on bacterial physiology and virulence gene expression through interaction with bacterial adrenergic receptors. Therefore, we hypothesize that the bacterial adrenergic receptors that are responsive towards epi and NE may in turn activate bacterial response towards these neurohormones, and consequently, microbes engineered to produce antagonists of stress-related signaling in the presence of increased levels of NE in the gut lumen may counteract downstream responses on central and peripheral systems.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 24, 2019
- Source ID
- FA23861814058
Entities
People
- Matthew Chang
Organizations
- Air Force Office of Scientific Research
- National University of Singapore
- United States Air Force