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Infection and Immunity, July 2006, p. 3765-3772, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.01413-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Escherichia coli Cytotoxic Necrotizing Factor 1 Blocks Cell Cycle G₂/M Transition in Uroepithelial Cells

Loredana Falzano,^1, Perla Filippini,^2, Sara Travaglione,¹ Alessandro Giamboi Miraglia,¹ Alessia Fabbri,¹ and Carla Fiorentini^1*

Department of Drug Research and Evaluation,¹ Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy²

Received 31 August 2005/ Returned for modification 19 December 2005/ Accepted 3 April 2006

Evidence is accumulating that a growing number of bacterial toxins act by modulating the eukaryotic cell cycle machinery. In this context, we provide evidence that a protein toxin named cytotoxic necrotizing factor 1 (CNF1) from uropathogenic Escherichia coli is able to block cell cycle G₂/M transition in the uroepithelial cell line T24. CNF1 permanently activates the small GTP-binding proteins of the Rho family that, beside controlling the actin cytoskeleton organization, also play a pivotal role in a large number of other cellular processes, including cell cycle regulation. The results reported here show that CNF1 is able to induce the accumulation of cells in the G₂/M phase by sequestering cyclin B1 in the cytoplasm and down-regulating its expression. The possible role played by the Rho GTPases in the toxin-induced cell cycle deregulation has been investigated and discussed. The activity of CNF1 on cell cycle progression can offer a novel view of E. coli pathogenicity.

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* Corresponding author. Mailing address: Department of Drug Research and Evaluation, Viale Regina Elena 299 00161, Rome, Italy. Phone: 39 0649903006. Fax: 39 0649903691. E-mail: carla.fiorentini{at}iss.it.

Editor: V. J. DiRita

L.F. and P.F. contributed equally to this work.

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Infection and Immunity, July 2006, p. 3765-3772, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.01413-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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