the biology of the cytolethal distending toxins的生物学cytolethal向外毒素.pdf

Toxins 2011, 3, 172-190; doi:10.3390/toxins3030172 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review The Biology of the Cytolethal Distending Toxins Lina Guerra, Ximena Cortes-Bratti, Riccardo Guidi and Teresa Frisan * Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden; E-Mails: lina.guerra@ki.se (L.G.); ximena.cortes.bratti@ki.se (X.C.-B.); riccardo.guidi@ki.se (R.G.) * Author to whom correspondence should be addressed; E-Mail: teresa.frisan@ki.se; Tel.: +46-8 Fax: +46-8-337412. Received: 17 January 2011; in revised form: 14 February 2011 / Accepted: 22 February 2011 / Published: 7 March 2011 Abstract: The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B2 toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi comple