Oligosaccharides may be an effective treatment or prophylaxis for gastrointestinal pathogeny. However, we foresee two significant barriers: little is known about the structure activity relationship between oligosaccharides and their targets, and preparation of oligosaccharides in quantities large enough for preclinical studies is a significant step in developing them for use as antimicrobial agents. Large enough quantities of oligosaccharides need to be synthesized to undergo safety studies, dose- ranging, and efficacy trials in infants and children who are at high risk of exposure to gastrointestinal pathogens. Furthermore, ready synthesis of analogs of these oligosaccharides containing modified and alternative monomers is required to study the structure activity relationship. Additionally, access to such analogs would allow for the discovery of novel antimicrobial oligos with perhaps different activity or specificity. A promising approach to synthesizing oligosaccharides and analogs in sufficient quantities for preclinical and clinical testing is using glycosyltransferases in vitro with simple starting materials such as monosaccharides or readily available polysaccharides and nucleotide activated sugars.
Intestinal pathogens such as E. coli O157:H7 cause a significant number of serious illnesses and death worldwide. The proposed research seeks to develop novel oligosaccharide based treatments against intestinal pathogens.
