A recombinant probiotic for treatment and prevention of cholera

被引:65
作者
Focareta, Antonio [1 ]
Paton, James C. [1 ]
Morona, Renato [1 ]
Cook, Jan [1 ]
Paton, Adrienne W. [1 ]
机构
[1] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia
基金
英国医学研究理事会; 澳大利亚研究理事会;
关键词
D O I
10.1053/j.gastro.2006.02.005
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: We have developed a therapeutic strategy based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. In the present study, this has been applied to the development of a recombinant probiotic for treatment and prevention of cholera, caused by Vibrio cholerae. Methods: We expressed glycosyltransferase genes from Neisseria gonorrhoeae and Campylobacter jejuni in a harmless Escherichia coli strain, resulting in production of a chimeric lipopolysaccharide terminating in a mimic of the ganglioside GMj(1). Results: The recombinant bacterium was capable of binding cholera toxin, a sine qua non of virulence, with high avidity; when tested with purified cholera toxin, it was capable of adsorbing > 5% of its own weight of toxin in vitro. Administration of the GM(1)-expressing probiotic also protected infant mice against challenge with virulent V cholerae, even when treatment was delayed until after establishment of infection. When treatment commenced 1 hour after challenge, 12 of 12 mice given the probiotic survived, compared with only 1 of 12 for control mice (P <.0000:1). Conclusions: Toxin-binding probiotics such as that described here have considerable potential for prophylaxis and treatment of cholera in humans.
引用
收藏
页码:1688 / 1695
页数:8
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