Abstract
Abstract Recent studies have explored the possibility of using microorganisms to synthesize and deliver therapeutics for the treatment of gastrointestinal disorders. Probiotic organisms, particularly the eukaryotic probiotic yeast Saccharomyces boulardii, may be well suited for this task given their current clinical applications for the treatment of gastrointestinal infections and inflammatory bowel diseases. Saccharomyces is furthermore capable of performing eukaryotic post translational modifications and can thus be made to express a wide array of therapeutic proteins. In order to increase the ease with which S. boulardii can be transformed to express recombinant protein, we developed auxotrophic mutant strains of S. boulardii using UV mutagenesis. Unlike wild type S. boulardii, these mutant S. boulardii can be genetically manipulated without reliance on antibiotic selection. These mutants also show a similar profile of resistance to conditions found in the gut, such as low pH and bile acid salts, relative to wild type S. boulardii. Critically, we demonstrate through oral gavage experiments that viable mutant S. boulardii recovered from murine gastrointestinal immune tissues continue to express recombinant protein. These mutant S. boulardii will thus permit studies to evaluate the ability of eukaryotic probiotics to deliver oral recombinant therapeutics and provide adjunctive therapy for the treatment of gastrointestinal disorders.
Published Version
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