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Infection and Immunity, March 2001, p. 1389-1393, Vol. 69, No. 3
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.
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
*
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.
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