Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition.
Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are closely related pathogens. Both use a type III secretion system (TTSS) encoded by the 'locus of enterocyte effacement' (LEE) to subvert and attach to epithelial cells through the injection of a repertoire of effector molecules. Here, we report the identification of a new TTSS translocated effector molecule called Cif, which blocks cell cycle G2/M transition and induces the formation of stress fibres through the recruitment of focal adhesions. Cif is not encoded by the LEE but by a lambdoid prophage present in EPEC and EHEC. A cif mutant causes localized effacement of microvilli and intimately attaches to the host cell surface, but is defective in the ability to block mitosis. When expressed in TTSS competent LEE-positive pathogens, Cif is injected into the infected epithelial cells. These cells arrested at the G2/M phase displayed accumulation of inactive phosphorylated Cdk1. In conclusion, Cif is a new member of a growing family of bacterial cyclomodulins that subvert the host eukaryotic cell cycle.
Marchès
Olivier
O
UMR 1225, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
Ledger
Terence Neil
TN
Boury
Michèle
M
Ohara
Masaru
M
Tu
Xuanlin
X
Goffaux
Frédéric
F
Mainil
Jacques
J
Rosenshine
Ilan
I
Sugai
Motoyuki
M
De Rycke
Jean
J
Oswald
Eric
E
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D010582:Bacteriophage lambda; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D019453:Escherichia coli O157 / Q000378:metabolism / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D008969:Molecular Sequence Data; D009154:Mutation; D039002:Prophages
D000199:Actins; C481998:Cif protein, E coli; D029968:Escherichia coli Proteins; D016203:CDC2 Protein Kinase