Two distinct cytotoxic activities of subtilase cytotoxin produced by shiga-toxigenic Escherichia coli.

Abstract:

: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 microg/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 approximately 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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Morinaga N,Yahiro K,Matsuura G,Watanabe M,Nomura F,Moss J,Noda M

doi

10.1128/IAI.01336-06

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

488-96

issue

1

eissn

0019-9567

issn

1098-5522

pii

IAI.01336-06

journal_volume

75

pub_type

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