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Infection and Immunity, January 2009, p. 492-500, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00962-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cytolethal Distending Toxin Type I and Type IV Genes Are Framed with Lambdoid Prophage Genes in Extraintestinal Pathogenic Escherichia coli {triangledown}

István Tóth,1* Jean-Philippe Nougayrède,2,3 Ulrich Dobrindt,4 Terence Neil Ledger,2,3 Michèle Boury,2,3 Stefano Morabito,5 Tamaki Fujiwara,6 Motoyuki Sugai,6 Jörg Hacker,7 and Eric Oswald2,3*

Veterinary Medical Research Institute of the Hungarian Academy of Sciences, Budapest, Hungary,1 INRA, UMR1225, F-31076 Toulouse, France,2 Université de Toulouse, ENVT, UMR1225, F-31076 Toulouse, France,3 Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany,4 Laboratorio di Medicina Veterinaria, Istituto Superiore di Sanità, Rome, Italy,5 Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan,6 Robert-Koch-Institute, Berlin, Germany7

Received 31 July 2008/ Returned for modification 17 September 2008/ Accepted 23 October 2008

Five types of cytolethal distending toxin (CDT-I to CDT-V) have been identified in Escherichia coli. In the present study we cloned and sequenced the cdt-IV operon and flanking region from a porcine extraintestinal pathogenic E. coli (ExPEC) strain belonging to serogroup O75. We confirmed that similar to other CDTs, CDT-IV induced phosphorylation of host histone H2AX, a sensitive marker of DNA double-strand breaks, and blocked the HeLa cell cycle at the G2-M transition. The cdt-IV genes were framed by lambdoid prophage genes. We cloned and sequenced the cdt-I operon and flanking regions from a human ExPEC O18:K1:H7 strain and observed that cdt-I genes were also flanked by lambdoid prophage genes. PCR studies indicated that a gene coding for a putative protease was always associated with the cdtC-IV gene but was not associated with cdtC genes in strains producing CDT-I, CDT-III, and CDT-V. Our results suggest that the cdt-I and cdt-IV genes might have been acquired from a common ancestor by phage transduction and evolved in their bacterial hosts. The lysogenic bacteriophages have the potential to carry nonessential "cargo" genes or "morons" and therefore play a crucial role in the generation of genetic diversity within ExPEC.

* Corresponding author. Mailing address for Eric Oswald: UMR1225 Interactions Hôtes-Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse, France. Phone: 33(0)5-61-19-39-91. Fax: 33(0)5-61-19-39-75. E-mail: e.oswald{at}envt.fr. Mailing address for István Tóth: Veterinary Medical Research Institute of the Hungarian Academy of Sciences, Hungaria Str. 21, 1143 Budapest, Hungary. Phone: 36-1-2522455. Fax: 36-1-2521069. E-mail: Tothi{at}vmri.hu

{triangledown} Published ahead of print on 3 November 2008.

Editor: S. R. Blanke

Infection and Immunity, January 2009, p. 492-500, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.00962-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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