Designer Probiotics and Enteric Cytoprotection

Abstract

Binding of bacterial toxins or adhesins to oligosaccharide receptors on the surface of eukaryotic cells is a crucial step in the pathogenesis of many infectious diseases. Thus, blockade of such interactions is a promising anti-infective strategy. This can be achieved by engineering expression of molecular mimics of host oligosaccharides on the surface of probiotic bacteria. The outer core region of the lipopolysaccharide (LPS) of harmless Gram-negative bacteria, for example, can be manipulated by expression of cloned heterologous glycosyltransferases. The resultant chimeric LPS molecules are incorporated into the outer membrane by the normal assembly route, and are presented as a closely packed 2-D array of receptor mimics, capable of forming multivalent, high-avidity interactions with their cognate ligands. For enteric infections, oral administration of such receptor-mimic probiotics will bind and neutralize toxins in the gut lumen, or interfere with adherence of pathogens to the intestinal epithelium, thereby preventing disease. © 2011 Springer Science+Business Media B.V.