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Infection and Immunity, July 2005, p. 4432-4436, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4432-4436.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Protective Immunization of Mice with an Active-Site Mutant of Subtilase Cytotoxin of Shiga Toxin-Producing Escherichia coli

School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia

Received 29 November 2004/ Returned for modification 3 February 2005/ Accepted 17 February 2005

We have recently described a novel AB₅ cytotoxin produced by certain Shiga toxin-producing Escherichia coli strains. The A subunit of this toxin is a subtilase-like serine protease, while the B pentamer mediates binding to host cell glycolipid receptors. The subtilase cytotoxin is lethal for mice, causing extensive microvascular thrombosis as well as necrosis in the brain, kidneys, and liver. In the present study, we have immunized mice with a purified derivative of the toxin with a Ser₂₇₂ Ala mutation in the A subunit which abolishes cytotoxicity. This elicited strong antibody responses, as judged by enzyme-linked immunosorbent assay, which conferred protection against intraperitoneal challenge with purified toxin. Immunized mice were also protected from weight loss resulting from oral challenge with an E. coli K-12 clone expressing the active toxin.

Editor: J. N. Weiser

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