In Vitro Assessment of Chemically Modified Probiotic Bacteria as Receptor-Mimic Decoys for Cholera Toxin B Subunit

Abstract

Gastrointestinal infections remain a major cause of morbidity and mortality worldwide. Conventional antibiotic treatment can be ineffective or inappropriate in some settings, particularly in the context of increasing antimicrobi-al resistance. In many enteric infections, an early step in pathogenesis involves binding of pathogens or their toxins to oligosaccharide receptors on host-cell surfaces, making these interactions attractive targets for antimicrobial strategies that do not rely on conventional antibiotics. Here, we developed a non-recombinant, microbiome-based chemical engineering approach in which cholesteryl-peptides serve as flexible chemical scaffolds for displaying GM1 receptor mimics on probiotic bacteria. The GM1-cholesteryl-peptides generated surface-accessible GM1 on both the Gram-positive probiotic Lactobacillus reuteri DSM 17938 and the Gram-negative probiotic Escherichia coli Nissle 1917. The resulting GM1-decorated bacteria showed concentration-dependent binding and sequestration of cholera toxin B subunit (CTB) in vitro and reduced CTB binding to Vero cells. These findings establish an in vitro proof-of-concept for a modular, non-recombinant bacterial decoy platform and may provide a basis for the future development of receptor-mimic strategies against toxin-mediated gastrointestinal infections.