title: A new cytolethal distending toxin (CDT) from Escherichia coli producing CNF2 blocks HeLa cell division in G2/M phase.
abstract: Escherichia coli strain 1404, isolated from a septicaemic calf, carries a transferable plasmid called pVir which codes for the cytotoxic necrotizing factor type 2 (CNF2). A 4h interaction between strain 1404 and HeLa cells induced the formation of giant mononucleated cells blocked in G2/M phase. Mating experiments between strain 1404 and a non-pathogenic recipient strain demonstrated that the factor(s) encoded by pVir mediated the cell-cycle arrest. A 3.3 kb DNA fragment isolated from a DNA bank of pVir was shown to code for the factor(s) causing the cell-cycle arrest. Nucleotide sequence analysis revealed the presence of three genes encoding proteins sharing significant amino acid homology with the cytolethal distending toxins (CDTs) previously isolated from E. coli, Campylobacter jejuni and Shigella dysenteriae. Southern hybridization experiments demonstrated that the pVir of other CNF2-producing E. coli strains contained sequences related to cdt. Although the amino acid sequences amongst CDT diverged significantly, the two other CDTs previously isolated from E. coli were also able to block the HeLa cell cycle. In conclusion, this study demonstrates the mode of action of CDT and will help us to elucidate the role of this emerging toxin family in microbial pathogenesis.
authors.affiliation: Unité associée de Microbiologie Moléculaire, Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire de Toulouse, France.
authors.forename: S Y
authors.initials: SY
authors.lastname: Pérès
authors.forename: O
authors.initials: O
authors.lastname: Marchès
authors.forename: F
authors.initials: F
authors.lastname: Daigle
authors.forename: J P
authors.initials: JP
authors.lastname: Nougayrède
authors.forename: F
authors.initials: F
authors.lastname: Herault
authors.forename: C
authors.initials: C
authors.lastname: Tasca
authors.forename: J
authors.initials: J
authors.lastname: De Rycke
authors.forename: E
authors.initials: E
authors.lastname: Oswald
mesh_terms: D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D003603:Cytotoxins / Q000096:biosynthesis*; D004269:DNA, Bacterial; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins; D005144:F Factor; D016195:G2 Phase; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data
chemical_list: D001427:Bacterial Toxins; D003603:Cytotoxins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C067044:cytolethal distending toxin; C086995:cytotoxic necrotizing factor type 2