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Infection and Immunity, April 2006, p. 2022-2030, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2022-2030.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Active Cytotoxic Necrotizing Factor 1 Associated with Outer Membrane Vesicles from Uropathogenic Escherichia coli

J. Clavin Kouokam,1,2 Sun Nyunt Wai,1* Maria Fällman,1 Ulrich Dobrindt,2 Jörg Hacker,2 and Bernt Eric Uhlin1*

Department of Molecular Biology, Umeå University, Umeå, Sweden,1 Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany2

Received 28 October 2005/ Returned for modification 6 December 2005/ Accepted 4 January 2006

Cytotoxic necrotizing factor type 1 (CNF1) is one of the virulence factors produced by uropathogenic Escherichia coli (UPEC). How this toxin is translocated from the bacterial cytoplasm to the surrounding environment is not well understood. Our data suggest that CNF1 may be regarded as a secreted protein, since it could be detected in culture supernatants. Furthermore, we found that CNF1 was tightly associated to outer membrane vesicles, suggesting that such vesicles play a role in the secretion of this protein. Interestingly, vesicle samples containing CNF1 could exert the effects known for this protein on HeLa cell cultures, showing that CNF1 is transported by vesicles in its active form. Taken together, our results strongly suggest that outer membrane vesicles could be a means for the bacteria to deliver CNF1 to the environment and to the infected tissue. In addition, our results indicate that the histone-like nucleoid structuring protein H-NS has a role in the downregulation of CNF1 production and that it affects the outer membrane vesicle release in UPEC strain J96.

* Corresponding author. Mailing address: Department of Molecular Biology, Umeå University, S-901 87 Umeå, Sweden. Phone for Bernt Eric Uhlin: 46 90 785 6731. Fax: 46 90 77 2630. E-mail: bernt.eric.uhlin{at}molbiol.umu.se. Phone for Sun Nyunt Wai: 46 90 785 6704. Fax: 46 90 77 2630. E-mail: sun.nyunt.wai{at}molbiol.umu.se.

Editor: J. T. Barbieri

Infection and Immunity, April 2006, p. 2022-2030, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2022-2030.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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