Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G(1) and G(2) cell cycle arrests, accumulation of the cyclin-dependent kinase inhibitors (CKIs) p21(waf1/cip1) and p27(kip1) and formation of actin stress fibres. The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad. Here we report the discovery and characterization of four Cif homologs encoded by different pathogenic or symbiotic bacteria isolated from vertebrates or invertebrates. Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli. Although these Cif homologs are remarkably divergent in primary sequence, the catalytic triad is strictly conserved and was shown to be crucial for cell cycle arrest, cytoskeleton reorganization and CKIs accumulation. These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans.
Jubelin
Grégory
G
INRA, UMR1225, Toulouse, France.
Chavez
Carolina Varela
CV
Taieb
Frédéric
F
Banfield
Mark J
MJ
Samba-Louaka
Ascel
A
Nobe
Rika
R
Nougayrède
Jean-Philippe
JP
Zumbihl
Robert
R
Givaudan
Alain
A
Escoubas
Jean-Michel
JM
Oswald
Eric
E
D000818:Animals; D001419:Bacteria / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000502:physiology*; D002453:Cell Cycle; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004754:Enterobacter / Q000737:chemistry* / Q000472:pathogenicity; D029968:Escherichia coli Proteins; D007399:Interphase; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; C481998:Cif protein, E coli; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D029968:Escherichia coli Proteins