Official Project Description
Substrate Selectivity in Commensal Gut Bacterial Sensors Hybrid Two-Component Sensor (HTCS) proteins help beneficial intestinal bacteria detect complex carbohydrates/fibers in their environment and upregulate Polysaccharide Uitilization Locus (PUL) genes which encode the transporters and enzymes required to degrade them into simpler sugars.
These sugars are fermented to produce beneficial metabolites like Short-Chain Fatty Acids (SFCAs) with several downstream benefits related to lipid and cholesterol metabolism, glucose regulation, and anti-inflammatory and anti-cancer effects. This project will study two β-propeller sensors in Bacterioides intestinalis, BACINT_04208 and BACINT_01044, with predicted preferences for soluble/unbranched versus insoluble/branched xylan-derived fibers.
Atomistic molecular dynamics simulations from docked poses with straight-chain xylan and branched arabinoxylan ligands will reveal binding/unbinding events to validate this hypothesized fiber selectivity in the sensors, along with specific residues implicated in ligand recognition.
The mechanistic insights from this project can support prebiotic and probiotic design and predictive microbiome models to address intestinal and metabolic health disorders like Inflammatory Bowel Diseases (IBDs) and Diabetes.