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Infection and Immunity, May 2009, p. 1835-1841, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01145-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cleavage of Escherichia coli Cytotoxic Necrotizing Factor 1 Is Required for Full Biologic Activity{triangledown}

Zeynep Knust,1,{dagger} Britta Blumenthal,2,{dagger} Klaus Aktories,1 and Gudula Schmidt1*

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Albert-Str. 25, 79104 Freiburg, Germany,1 Fakultät für Biologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany2

Received 15 September 2008/ Returned for modification 1 November 2008/ Accepted 13 February 2009

Cytotoxic necrotizing factor 1 (CNF1) is a protein toxin produced by pathogenic Escherichia coli strains. CNF1 constitutively activates small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. The toxin is taken up into mammalian cells by receptor-mediated endocytosis and is delivered from late endosomes into the cytosol. Here, we show that an approximately 55-kDa fragment of CNF1, which contains the catalytic domain and an additional part of the toxin, is present in the cytosol. The processing of this fragment requires an acidic pH and insertion of the toxin into the endosomal membrane. We define the cleavage site region as the region located between amino acids 532 and 544 of CNF1. The data provide insight into the complex mechanism of uptake of bacterial toxins into mammalian cells.

* Corresponding author. Mailing address: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Albert-Str. 25, 79104 Freiburg, Germany. Phone: (49) 761 203 5316. Fax: (49) 761 203 5311. E-mail: Gudula.Schmidt{at}pharmakol.uni-freiburg.de

{triangledown} Published ahead of print on 23 February 2009.

Editor: S. R. Blanke

{dagger} Z.K. and B.B. contributed equally to this study.

Infection and Immunity, May 2009, p. 1835-1841, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01145-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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