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Related Concept Videos

Antibiotic Selection00:57

Antibiotic Selection

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Related Experiment Video

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Programming Probiotics: Diet-Responsive Gene Expression and Colonization Control in Engineered S. boulardii.

Deniz Durmusoglu1, Daniel J Haller1, Ibrahim S Al'Abri1

  • 1Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States.

ACS Synthetic Biology
|May 24, 2024
PubMed
Summary

Engineered Saccharomyces boulardii (Sb) probiotics with inducible gene expression and controlled gut residence time. This allows precise control over therapeutic biomolecule delivery in the mammalian gut.

Keywords:
microbiomesynthetic biologyyeast

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Area of Science:

  • Microbiology
  • Synthetic Biology
  • Gastroenterology

Background:

  • Saccharomyces boulardii (Sb) is a eukaryotic probiotic with potential for delivering biomolecules to the gut.
  • Challenges exist in precisely controlling gene expression and gut residence time for Sb.

Purpose of the Study:

  • To develop ligand-responsive gene expression systems for Sb.
  • To engineer Sb for inducible gene expression and controlled gut residence time.

Main Methods:

  • Developed five ligand-responsive gene expression systems in Sb.
  • Repaired galactose metabolism in Sb.
  • Engineered AND logic gates and surface protein display systems.
  • Utilized dietary sugar for inducible protein production in mice.

Main Results:

  • Achieved inducible gene expression in Sb.
  • Demonstrated control over protein production and surface display in response to dietary sugar.
  • Expanded Sb's intestinal habitat by repairing galactose metabolism.
  • Established galactose-responsive control over Sb's gut residence time.

Conclusions:

  • Engineered Sb offers precise control over in vivo gene expression and localization.
  • This enables new strategies for targeted therapeutic delivery via probiotics.
  • The developed systems enhance the potential of Sb as a probiotic chassis.