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

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 antimicrobial 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. After incubation with the GM1-cholesteryl-peptides, GM1 signals accessible to the cholera toxin B subunit (CTB) were detected 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 CTB binding and sequestration 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.