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Recombinant bacteria expressing oligosaccharide receptor mimics for prevention of enteric infections

表达寡糖受体模拟物的重组细菌用于预防肠道感染

基本信息

批准号：
nhmrc : 250355
负责人：
A/Pr Renato Morona
金额：
$ 30.08万
依托单位：
依托单位国家：
澳大利亚
项目类别：
NHMRC Development Grants
财政年份：
2002
资助国家：
澳大利亚
起止时间：
2002-01-01 至 2004-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/recombinant-bacteria-expressing-enteric-infections/81133
关键词：
Recombinant bacteria expressing oligosaccharide receptor

项目摘要

Gastrointestinal infectious diseases kill more than 3 million people each year. The principal microbial pathogens responsible for these infections are known to exploit oligosaccharides on the surface of host cells as receptors for ahesins or toxins. We have developed (and patented) a novel anti-infective strategy, based on mimicry of oligosaccharide receptors for toxins and adhesins produced by enteric pathogens on the surface of harmless carrier bacteria. Oral administration of such recombinant probiotics has the potential to prevent enteric infections by binding and neutralizing toxins in the gut lumen and by blocking adherence of the pathogen to intestinal epithelial cells. As a prototypic example, we have developed a bacterium capable of preventing the serious consequences of Shiga toxigenic Escherichia coli (STEC) infections; this agent binds Shiga toxin with very high efficiency and is 100% protective in animal models. The strategy has very broad applications, however, and receptors for virtually any pathogen can be mimicked by expression of appropriate glycosyl transferases in a suitable harmless host bacterium. This proposal involves extension of our existing work to develop therapeutic agents for other important life threatening diarrhoeal diseases including cholera, travellers' diarrhoea, dysentery, antibiotic-associated colitis, rotavirus, etc.

胃肠道传染病每年造成300多万人死亡。已知引起这些感染的主要微生物病原体利用宿主细胞表面上的寡糖作为ahesin或毒素的受体。我们开发了一种新型抗感染策略（并获得专利），该策略基于对肠道病原体在无害载体细菌表面产生的毒素和粘附素的寡糖受体的模拟。口服施用这种重组益生菌具有通过结合和中和肠腔中的毒素以及通过阻断病原体粘附于肠上皮细胞来预防肠道感染的潜力。作为一个典型的例子，我们已经开发了一种能够预防滋贺致突变大肠杆菌（STEC）感染的严重后果的细菌;这种药物以非常高的效率结合滋贺毒素，在动物模型中具有100%的保护性。然而，该策略具有非常广泛的应用，并且几乎任何病原体的受体都可以通过在合适的无害宿主细菌中表达适当的糖基转移酶来模拟。这项建议涉及扩展我们现有的工作，以研制治疗其他严重威胁生命的肠道疾病的药物，包括霍乱、旅行者腹泻、痢疾、腹泻相关结肠炎、轮状病毒等。