title: Synthesis and assessment of globotriose-chitosan conjugate, a novel inhibitor of shiga toxins produced by Escherichia coli.
abstract: Shiga toxin (Stx)-producing Escherichia coli (STEC) causes diarrhea and colitis in humans that can develop into a life-threatening hemolytic uremic syndrome (HUS). Developing efficient means of controlling STEC diseases, for which no drugs or vaccines are currently available, remains a high priority. We report here the construction and development of chitosan conjugates bearing the Stx ligand trisaccharide globotriose to demonstrate their potential as STEC disease treatment agents. The synthesis was accomplished by grafting a globotriose derivative containing an aldehyde-functionalized aglycone to chitosan amino groups. The obtained globotriose-chitosan conjugate bound with high affinity to Stx and efficiently neutralized its toxicity on Vero cells. Moreover, Stx levels in the gut of infected mice receiving oral doses of the conjugate were greatly diminished, enabling the mice to resist a fatal STEC challenge. The conjugate appears to function as a Stx adsorbent in the gut, preventing toxin entry into the bloodstream and consequent development of HUS. As such, the conjugate could act as a novel agent against STEC disease.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. lixb@im.ac.cn
authors.forename: Xuebing
authors.initials: X
authors.lastname: Li
authors.forename: Peixing
authors.initials: P
authors.lastname: Wu
authors.forename: Shuihong
authors.initials: S
authors.lastname: Cheng
authors.forename: Xun
authors.initials: X
authors.lastname: Lv
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004927:Escherichia coli Infections / Q000382:microbiology / Q000517:prevention & control; D019453:Escherichia coli O157 / Q000378:metabolism*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D022603:Shiga Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014312:Trisaccharides / Q000737:chemistry* / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D022603:Shiga Toxins; D014312:Trisaccharides; C113460:globotriose; D048271:Chitosan