Clostridium difficile toxin B

Immunotherapy

Probiotic

Antibiotics

Bacteria

Monoclonal antibody

Biology

Microbiology

Gene

Antibody

Virology

Immunology

Toxin

Saccharomyces boulardii

Antitoxin

Clostridium difficile

Genetics

Biochemistry

Virulence

Medicine

Immune system

Antibiotic resistance

Clostridium difficile toxin A

Science Translational Medicine

Antibiotic-resistant Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the colon and is responsible for more than 29,000 deaths in the United States each year. Hence, C. difficile infection (CDI) poses an urgent threat to public health. Antibody-mediated neutralization of TcdA and TcdB toxins, the major virulence factors of CDI, represents an effective strategy to combat the disease without invoking antibiotic resistance. However, current antitoxin approaches are mostly based on parenteral infusion of monoclonal antibodies that are costly, narrow spectrum, and not optimized against the intestinal disease. Here, we engineered probiotic Saccharomyces boulardii to constitutively secrete a single tetra-specific antibody that potently and broadly neutralized both toxins and demonstrated protection against primary and recurrent CDI in both prophylactic and therapeutic mouse models of disease. This yeast immunotherapy is orally administered, can be used concurrently with antibiotics, and may have potential as a prophylactic against CDI risk and as a therapeutic for patients with CDI.

A probiotic yeast-based immunotherapy against <i>Clostridioides difficile</i> infection

A probiotic yeast-based immunotherapy against Clostridioides difficile infection