Adherence of pathogens to their host cells is the obligatory first step of infection and is frequently mediated by specific molecular interactions [1][2]. Virulent Campylobacter species, Vibrio cholerae, enteropathogenic E.coli (EPEC), enterohemorrhagic E.coli (EHEC) and pathogenic strains of Norwalk virus, the leading bacterial and viral causes of human infectious diarrhea [3], adhere to gut epithelial surfaces through binding to 1(1,2) fucosylated cellular receptors[4][5]. 1(1,2) fucosylated glycans, which are abundant in human breast milk[6][7], have been shown both in vitro and in vivo effectively to prevent binding and infection by these pathogens[4][5]. These molecules therefore represent a new class of agent with potential to prevent infectious diarrhea, a condition that is the cause annually of over 2 million deaths worldwide [8]. However the production of 1(1,2) fucosylated glycans as anti-infective agents in sufficient quantities to impact global diarrhea incidence remains a significant challenge. Chemical syntheses are possible, but are limited by stereo-specificity issues, product impurities, and high overall cost[9][10][11]. In vitro enzymatic syntheses are also possible but are limited by a requirement for expensive nucleotide-sugar precursors. Glycosyn Inc.
Public Health Relevance
Worldwide, infectious diarrhea[12] is responsible for approximately 20% of all mortality in children under the age of 5, and for an estimated 2 million deaths annually[8]. In the developing world bacterial infections cause more than 50% of all cases of diarrhea, and of these, infections by Campylobacter and diarrheagenic E.coli together account for about half. Campylobacter is the most common cause of culture-proven bacterial gastroenteritis in both developed and developing countries, and is responsible for 400 to 500 million cases of diarrhea each year. By far the highest incidence of Campylobacter infections is in children <5 yrs of age[13][14][15]. Unfortunately, prevention and treatment options for bacterial diarrhea are limited. Vaccines are currently unavailable, and if developed, would be costly and of limited availability in rural poor populations where unmet need is highest. Moreover vaccines are typically pathogen-specific, but infectious diarrhea can be caused by numerous diverse pathogens. The use of antibiotics for treatment of diarrhea is also becoming increasingly problematic, since such use is driving the emergence of resistant strains. For example, clinical isolates of Campylobacter are now often resistant to quinolones [16] and erythromycin-resistant strains are rapidly emerging [17]. Conventional antimicrobial agents are designed to inhibit a pathogen
