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Infection and Immunity, January 2007, p. 488-496, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01336-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Two Distinct Cytotoxic Activities of Subtilase Cytotoxin Produced by Shiga-Toxigenic Escherichia coli

Department of Molecular Infectiology,¹ Department of Pediatric Surgery,² Department of Molecular Diagnosis and Clinical Genetics, Graduate School of Medicine,⁴ Division of Laboratory Medicine, Chiba University Hospital, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan,³ Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1590⁵

Received 21 August 2006/ Returned for modification 22 September 2006/ Accepted 13 October 2006

Subtilase cytotoxin (SubAB) is a recently identified AB5 subunit toxin produced by Shiga-toxigenic Escherichia coli. The A subunit is thought to be a subtilase-like, serine protease, whereas the B subunit binds to the toxin receptor on the cell surface. We cloned the genes from a clinical isolate; the toxin was produced as His-tagged proteins. SubAB induced vacuolation at concentrations greater than 1 µg/ml after 8 h, in addition to the reported cytotoxicity induced at a ng/ml level after 48 h. Vacuolation was induced with the B, but not the A, subunit and was dependent on V-type ATPase. The cytotoxicity of SubAB at low concentrations was associated with the inhibition of protein synthesis; the 50% inhibitory dose was 1 ng/ml. The A subunit, containing serine 272, which is thought to be a part of the catalytic triad of a subtilase-like serine protease, plus the B subunit was necessary for this activity, both in vivo and in vitro. SubAB did not cleave azocasein, bovine serum albumin, ovalbumin, or synthetic peptides. These data suggest that SubAB is a unique AB toxin: first, the B subunit alone can induce vacuolation; second, the A subunit containing serine 272 plus the B subunit inhibited protein synthesis, both in vivo and in vitro; and third, the A subunit proteolytic activity may have a strict range of substrate specificity.

Published ahead of print on 13 November 2006.

Editor: A. D. O'Brien