In Vitro Assessment of chemically-modified probiotics as toxin decoys for cholera infections

Abstract Gastrointestinal infections are a leading cause of death and morbidity worldwide. Antibiotics as current treatments are ineffective or not recommended due to the emergence of multidrug resistant organisms. The initial step of the pathogenesis for most of the enteric infections is the binding of the pathogen to oligosaccharide receptors on the surface of host cells, making these receptors attractive targets for novel antimicrobial strategies that do not rely on conventional antibiotics. Here, we developed an alternative therapeutic intervention based on a novel microbiome-based chemical engineering approach. We synthesized cholesteryl-peptides as flexible chemical scaffold for the presentation of carbohydrate GM1 mimic receptors in probiotic bacteria acting as a decoy for cholera toxin neutralization. The GM1-cholesteryl-peptides were stably embedded into the membranes of both gram positive and gram negative probiotics, Lactobacillus reuteri DSM and Escherichia coli Nissle 1917 respectively. The resulting GM1-coated probiotics demonstrated to quench nearly 100% of cholera toxin in vitro , functioning as decoys by preventing toxin binding to epithelial cells. The present study strongly suggests that our new and versatile biomimetic non-recombinant system could be employed to neutralize the functional effect of infections mediated by oligosaccharide receptors. Abstract Figure