Cyclomodulins: bacterial effectors that modulate the eukaryotic cell cycle.
Microbial pathogens have developed a variety of strategies to manipulate host-cell functions, presumably for their own benefit. We propose the term "cyclomodulins" to describe the growing family of bacterial toxins and effectors that interfere with the eukaryotic cell cycle. Inhibitory cyclomodulins, such as cytolethal distending toxins (CDTs) and the cycle inhibiting factor (Cif), block mitosis and might constitute powerful weapons for immune evasion by inhibiting clonal expansion of lymphocytes. Cell-cycle inhibitors might also impair epithelial-barrier integrity, allowing the entry of pathogenic bacteria into the body or prolonging their local existence by blocking the shedding of epithelia. Conversely, cyclomodulins that promote cellular proliferation, such as the cytotoxic necrotizing factor (CNF), exemplify another subversion mechanism by interfering with pathways of cell differentiation and development. The role of these cyclomodulins in bacterial virulence and carcinogenesis awaits further study and will delineate new perspectives in basic research and therapeutic applications.
Nougayrède
Jean-Philippe
JP
UMR 1225 Interactions Hôtes-Agents Pathogènes, Ecole Nationale Vétérinaire, 23 chemin des Capelles BP 87614 31076, Toulouse Cedex 3, France.
Taieb
Frédéric
F
De Rycke
Jean
J
Oswald
Eric
E
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D002453:Cell Cycle / Q000502:physiology; D029968:Escherichia coli Proteins / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans
D001427:Bacterial Toxins; C481998:Cif protein, E coli; D029968:Escherichia coli Proteins; C067044:cytolethal distending toxin; C060296:cytotoxic necrotizing factor type 1