Superresolution imaging captures carbohydrate utilization dynamics in human gut symbionts

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Gut microbes are crucial for human health, metabolizing nutrients like carbohydrates using enzymes absent in humans.
• The specific molecular mechanisms of carbohydrate breakdown by gut symbionts remain largely unknown.
• Understanding these processes is key to developing targeted therapies for gut health.

Purpose of the Study:

• To elucidate the real-time molecular assembly and function of the starch utilization system (Sus) in Bacteroides thetaiotaomicron.
• To provide a mechanistic understanding of glycan catabolism in a prominent human gut symbiont.
• To establish a foundation for manipulating gut microbial populations for therapeutic benefit.

Main Methods:

• Live-cell superresolution fluorescence imaging to visualize protein dynamics.
• Single-molecule analysis of outer membrane protein interactions in real time.
• Construction and analysis of Sus protein knockout strains in anaerobic conditions.

Main Results:

• Starch dynamically recruits Sus proteins, forming an external scaffold for complex assembly on the bacterial membrane.
• The stoichiometry and dynamics of starch-induced Sus complex assembly were characterized at the molecular scale.
• A detailed mechanism for Sus complex assembly in live anaerobic cells was elucidated using nanometer-scale resolution.

Conclusions:

• The study provides the first dynamic model of Sus complex assembly and function during starch catabolism.
• These findings offer mechanistic insights into a conserved nutrient uptake strategy prevalent in human gut Bacteroidetes.
• Understanding this system can inform the development of dietary or pharmaceutical interventions to modulate gut microbiota for improved health.