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Infection and Immunity, March 2001, p. 1389-1393, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1389-1393.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Oral Administration of Formaldehyde-Killed Recombinant Bacteria Expressing a Mimic of the Shiga Toxin Receptor Protects Mice from Fatal Challenge with Shiga-Toxigenic Escherichia coli

James C. Paton,1,2 Trisha J. Rogers,1,2 Renato Morona,2 and Adrienne W. Paton1,2,*

Molecular Microbiology Unit, Women's and Children's Hospital, North Adelaide, South Australia 5006,1 and Department of Molecular Biosciences, Adelaide University, Adelaide, South Australia 5005,2 Australia

Received 6 September 2000/Returned for modification 12 October 2000/Accepted 28 November 2000

Gastrointestinal disease caused by Shiga toxin-producing Escherichia coli (STEC) is frequently complicated by life-threatening toxin-induced systemic sequelae, including the hemolytic uremic syndrome. We previously constructed a recombinant bacterium displaying a Shiga toxin receptor mimic on its surface which neutralized Shiga toxins with very high efficiency. Moreover, oral administration of the live bacterium completely protected mice from challenge with virulent STEC. In this study, we investigated the protective capacity of formaldehyde-killed receptor mimic bacteria, as these are likely to be safer for administration to humans. The killed bacteria completely protected STEC-challenged mice when administered three times daily; incomplete protection was achieved using two doses per day. Commencement of therapy could be delayed for up to 48 h after challenge without diminishing protection, depending on the virulence of the challenge strain. Thus, administration of this agent early in the course of human STEC disease may prevent progression to life-threatening complications.


* Corresponding author. Mailing address: Department of Molecular Biosciences, Adelaide University, Adelaide, S.A. 5005, Australia. Phone: 61-8-83037552. Fax: 61-8-83033262. E-mail: adrienne.paton{at}adelaide.edu.au.


Infection and Immunity, March 2001, p. 1389-1393, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1389-1393.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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