{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:26:18Z","timestamp":1791606378008,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2011,3,7]],"date-time":"2011-03-07T00:00:00Z","timestamp":1299456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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 complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and\/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.<\/jats:p>","DOI":"10.3390\/toxins3030172","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T09:11:15Z","timestamp":1299575475000},"page":"172-190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":137,"title":["The Biology of the Cytolethal Distending Toxins"],"prefix":"10.3390","volume":"3","author":[{"given":"Lina","family":"Guerra","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximena","family":"Cortes-Bratti","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Guidi","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Frisan","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden, Box 285, S-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2011,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1126\/science.1127059","article-title":"Escherichia coli induces DNA double-strand breaks in eukaryotic cells","volume":"313","author":"Nougayrede","year":"2006","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/S0041-0101(01)00159-3","article-title":"The cytolethal distending toxins induce DNA damage and cell cycle arrest","volume":"39","author":"Frisan","year":"2001","journal-title":"Toxicon"},{"key":"ref_3","unstructured":"Alouf, J., and Popoff, M. (2006). The Comprehensive Sourcebook of Bacterial Protein Toxins, CPL Press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nature02532","article-title":"Assembly and function of a bacterial genotoxin","volume":"429","author":"Nesic","year":"2004","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1046\/j.1365-2958.2000.02070.x","article-title":"DNAase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest","volume":"37","author":"Elwell","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1126\/science.290.5490.354","article-title":"A bacterial toxin that controls cell cycle progression as a deoxyribonuclease I-like protein","volume":"290","author":"Galan","year":"2000","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5752","DOI":"10.1128\/IAI.69.9.5752-5759.2001","article-title":"Cytolethal distending toxin demonstrates genotoxic activity in a yeast model","volume":"69","author":"Hassane","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1462-5822.2005.00520.x","article-title":"Cellular internalization of cytolethal distending toxin: A new end to a known pathway","volume":"7","author":"Guerra","year":"2005","journal-title":"Cell. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/prot.20767","article-title":"Comparative structure-function analysis of cytolethal distending toxins","volume":"62","author":"Hu","year":"2006","journal-title":"Proteins"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1128\/IAI.00739-05","article-title":"Biogenesis of the Actinobacillus actinomycetemcomitans cytolethal distending toxin holotoxin","volume":"74","author":"Ueno","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1128\/IAI.71.9.4883-4890.2003","article-title":"Interactions of Campylobacter jejuni cytolethal distending toxin subunits CdtA and CdtC with HeLa cells","volume":"71","author":"Lee","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1128\/IAI.73.4.2051-2060.2005","article-title":"Carbohydrate-binding specificity of the Escherichia coli cytolethal distending toxin CdtA-II and CdtC-II subunits","volume":"73","author":"McSweeney","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1128\/IAI.73.8.4846-4852.2005","article-title":"Involvement of ganglioside GM3 in G(2)\/M cell cycle arrest of human monocytic cells induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin","volume":"73","author":"Mise","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1046\/j.1462-5822.2002.00186.x","article-title":"Functional studies of the recombinant subunits of a cytolethal distending holotoxin","volume":"4","author":"Mao","year":"2002","journal-title":"Cell. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1099\/mic.0.27671-0","article-title":"Mechanism of internalization of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans","volume":"151","author":"Akifusa","year":"2005","journal-title":"Microbiology"},{"key":"ref_16","unstructured":"Frisan, T. (2011). Unpublished work."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/j.1462-5822.2005.00669.x","article-title":"Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal-distending toxin","volume":"8","author":"Besack","year":"2006","journal-title":"Cell. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1126\/science.1178955","article-title":"Haploid genetic screens in human cells identify host factors used by pathogens","volume":"326","author":"Carette","year":"2009","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18199","DOI":"10.1074\/jbc.M110.112912","article-title":"Cytolethal distending toxin family members are differentially affected by alterations in host glycans and membrane cholesterol","volume":"285","author":"Eshraghi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/35101607","article-title":"Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18","volume":"413","author":"Parkhill","year":"2001","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1073\/pnas.0400932101","article-title":"Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway","volume":"101","author":"Haghjoo","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.chom.2007.11.001","article-title":"Delivery of a Salmonella typhi exotoxin from a host intracellular compartment","volume":"3","author":"Spano","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6903","DOI":"10.1128\/IAI.68.12.6903-6911.2000","article-title":"Cellular internalization of cytolethal distending toxin from Haemophilus ducreyi","volume":"68","author":"Thelestam","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.bbamcr.2008.11.017","article-title":"A novel mode of translocation for cytolethal distending toxin","volume":"1793","author":"Guerra","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"50671","DOI":"10.1074\/jbc.M305062200","article-title":"An N-terminal segment of the active component of the bacterial genotoxin cytolethal distending toxin B (CDTB) directs CDTB into the nucleus","volume":"278","author":"Nishikubo","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1462-5822.2004.00373.x","article-title":"Nuclear localization of the Escherichia coli cytolethal distending toxin CdtB subunit","volume":"6","author":"McSweeney","year":"2004","journal-title":"Cell. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.tibs.2003.10.002","article-title":"The intracellular voyage of cholera toxin: going retro","volume":"28","author":"Lencer","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0966-842X(99)01537-1","article-title":"The cytolethal distending toxin family","volume":"7","author":"Pickett","year":"1999","journal-title":"Trends Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1074\/mcp.M700295-MCP200","article-title":"Proteomics characterization of outer membrane vesicles from the extraintestinal pathogenic Escherichia coli DeltatolR IHE3034 mutant","volume":"7","author":"Scorza","year":"2008","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/1471-2180-9-220","article-title":"Outer membrane vesicle-mediated release of cytolethal distending toxin (CDT) from Campylobacter jejuni","volume":"9","author":"Lindmark","year":"2009","journal-title":"BMC Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1046\/j.1462-5822.2003.00311.x","article-title":"The Haemophilus ducreyi cytolethal distending toxin induces DNA double strand breaks and promotes ATM-dependent activation of RhoA","volume":"5","author":"Frisan","year":"2003","journal-title":"Cell. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.1128\/IAI.69.5.3418-3422.2001","article-title":"Escherichia coli CdtB mediates cytolethal distending toxin cell cycle arrest","volume":"69","author":"Elwell","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1046\/j.1462-5822.2002.00174.x","article-title":"The Haemophilus ducreyi cytolethal distending toxin activates sensors of DNA damage and repair complexes in proliferating and non-proliferating cells","volume":"4","author":"Li","year":"2002","journal-title":"Cell. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/B978-0-12-380888-2.00003-0","article-title":"The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer","volume":"108","author":"Smith","year":"2010","journal-title":"Adv. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1126\/science.1140735","article-title":"An oncogene-induced DNA damage model for cancer development","volume":"319","author":"Halazonetis","year":"2008","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5088","DOI":"10.1128\/iai.65.12.5088-5095.1997","article-title":"Escherichia coli cytolethal distending toxin blocks the HeLa cell cycle at the G2\/M transition by preventing cdc2 protein kinase dephosphorylation and activation","volume":"65","author":"Comayras","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.4049\/jimmunol.162.8.4773","article-title":"Actinobacillus actinomycetemcomitans immunosuppressive protein is a member of the family of cytolethal distending toxins capable of causing a G2 arrest in human T cells","volume":"162","author":"Shenker","year":"1999","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6296","DOI":"10.1038\/sj.onc.1203007","article-title":"The bacterial cytolethal distending toxin (CDT) triggers a G2 cell cycle checkpoint in mammalian cells without preliminary induction of DNA strand breaks","volume":"18","author":"Sert","year":"1999","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1074\/jbc.M008527200","article-title":"The Haemophilus ducreyi cytolethal distending toxin induces cell cycle arrest and apoptosis via the DNA damage checkpoint pathways","volume":"276","author":"Karlsson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1128\/IAI.71.1.541-545.2003","article-title":"Campylobacter jejuni cytolethal distending toxin promotes DNA repair responses in normal human cells","volume":"71","author":"Hassane","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1600-0722.2004.00157.x","article-title":"Delivery of cytolethal distending toxin B induces cell cycle arrest and apoptosis in gingival squamous cell carcinoma in vitro","volume":"112","author":"Yamamoto","year":"2004","journal-title":"Eur. J. Oral. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1128\/IAI.70.2.528-534.2002","article-title":"p53-independent expression of p21(CIP1\/WAF1) in plasmacytic cells during G(2) cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin","volume":"70","author":"Sato","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e8924","DOI":"10.1371\/journal.pone.0008924","article-title":"Myc is required for activation of the ATM-dependent checkpoints in response to DNA damage","volume":"5","author":"Guerra","year":"2010","journal-title":"PLoS One"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1582-4934.2009.00862.x","article-title":"Bacterial Intoxication Evokes Cellular Senescence with Persistent DNA Damage and Cytokine Signaling","volume":"14","author":"Blazkova","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1128\/IAI.01321-06","article-title":"Genome-wide analysis of cellular response to bacterial genotoxin CdtB in yeast","volume":"75","author":"Kitagawa","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature03097","article-title":"Cell-cycle checkpoints and cancer","volume":"432","author":"Kastan","year":"2004","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrc1011","article-title":"ATM and related protein kinases: safeguarding genome integrity","volume":"3","author":"Shiloh","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6394","DOI":"10.1128\/IAI.67.12.6394-6402.1999","article-title":"Cytolethal distending toxin of Haemophilus ducreyi induces apoptotic death of Jurkat T cells","volume":"67","author":"Gelfanova","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1172\/JCI3831","article-title":"The cytolethal distending toxin from the chancroid bacterium Haemophilus ducreyi induces cell-cycle arrest in the G2 phase","volume":"103","author":"Thelestam","year":"1999","journal-title":"J. Clin. Invest."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e2254","DOI":"10.1371\/journal.pone.0002254","article-title":"A bacterial cytotoxin identifies the RhoA exchange factor Net1 as a key effector in the response to DNA damage","volume":"3","author":"Guerra","year":"2008","journal-title":"PLoS One"},{"key":"ref_51","unstructured":"Guerra, L., Guidi, R., Ilse, S., Callegari, S., Sompallae, R., Pickett, C.L., \u00c5str\u00f6m, S., Eisele, F., Wolf, D., Sj\u00f6gren, C., Masucci, M.G., and Frisan, T. Bacterial genotoxin triggers FEN1-dependent RhoA activation, cytoskeleton remodeling and cell survival. submitted for publication."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"435","DOI":"10.4049\/jimmunol.167.1.435","article-title":"Induction of apoptosis in human T cells by Actinobacillus actinomycetemcomitans cytolethal distending toxin is a consequence of G2 arrest of the cell cycle","volume":"167","author":"Shenker","year":"2001","journal-title":"J. Immun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1128\/IAI.72.2.871-879.2004","article-title":"Caspase-2 and caspase-7 are involved in cytolethal distending toxin-induced apoptosis in Jurkat and MOLT-4 T-cell lines","volume":"72","author":"Ohara","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1128\/IAI.01612-07","article-title":"Cytolethal distending toxin induces caspase-dependent and -independent cell death in MOLT-4 cells","volume":"76","author":"Ohara","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1128\/IAI.01227-08","article-title":"Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces apoptosis in nonproliferating macrophages by a phosphatase-independent mechanism","volume":"77","author":"Rabin","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.4049\/jimmunol.178.8.5099","article-title":"A novel mode of action for a microbial-derived immunotoxin: the cytolethal distending toxin subunit B exhibits phosphatidylinositol 3,4,5-triphosphate phosphatase activity","volume":"178","author":"Shenker","year":"2007","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/IAI.00857-09","article-title":"Cytolethal distending toxin from Aggregatibacter actinomycetemcomitans induces DNA damage, S\/G2 cell cycle arrest, and caspase- independent death in a Saccharomyces cerevisiae model","volume":"78","author":"Matangkasombut","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2006.02.016","article-title":"Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer","volume":"124","author":"Karin","year":"2006","journal-title":"Cell"},{"key":"ref_60","unstructured":"(1994). Schistosomes, Liver Flukes and Helicobacter Pylori."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/1097-0142(20001001)89:7<1431::AID-CNCR4>3.0.CO;2-5","article-title":"Detection of Helicobacter species in the liver of patients with and without primary liver carcinoma","volume":"89","author":"Avenaud","year":"2000","journal-title":"Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1053\/gast.2001.21382","article-title":"Helicobacter species identified in liver from patients with cholangiocarcinoma and hepatocellular carcinoma","volume":"120","author":"Nilsson","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1099\/0022-1317-49-5-473","article-title":"Characterisation of cytolethal distending toxin (CDT) mutants of Campylobacter jejuni","volume":"49","author":"Purdy","year":"2000","journal-title":"J. Med. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1172\/JCI26705","article-title":"MUC1 cell surface mucin is a critical element of the mucosal barrier to infection","volume":"117","author":"McAuley","year":"2007","journal-title":"J. Clin. Invest."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1128\/IAI.72.2.1116-1125.2004","article-title":"Gastroenteritis in NF-kappaB-deficient mice is produced with wild-type Camplyobacter jejuni but not with C. jejuni lacking cytolethal distending toxin despite persistent colonization with both strains","volume":"72","author":"Fox","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6535","DOI":"10.1128\/IAI.68.12.6535-6541.2000","article-title":"Campylobacter jejunic cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells","volume":"68","author":"Hickey","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1099\/0022-1317-49-6-525","article-title":"Identification of cdtB homologues and cytolethal distending toxin activity in enterohepatic Helicobacter spp","volume":"49","author":"Chien","year":"2000","journal-title":"J. Med. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1128\/IAI.73.6.3559-3567.2005","article-title":"Cytolethal distending toxin is essential for Helicobacter hepaticus colonization in outbred Swiss Webster mice","volume":"73","author":"Ge","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1128\/IAI.72.5.2521-2527.2004","article-title":"In vitro and in vivo characterization of Helicobacter hepaticus cytolethal distending toxin mutants","volume":"72","author":"Young","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1111\/j.1462-5822.2007.00939.x","article-title":"Bacterial cytolethal distending toxin promotes the development of dysplasia in a model of microbially induced hepatocarcinogenesis","volume":"9","author":"Ge","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1128\/CMR.8.3.357","article-title":"Chancroid and Haemophilus ducreyi: An update","volume":"8","author":"Trees","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1126\/science.276.5309.75","article-title":"Wound healing\u2014aiming for perfect skin regeneration","volume":"276","author":"Martin","year":"1997","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"11S","DOI":"10.1016\/S0002-9610(03)00296-4","article-title":"Understanding the role of immune regulation in wound healing","volume":"187","author":"Park","year":"2004","journal-title":"Am. J. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.micinf.2005.02.009","article-title":"The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid","volume":"7","author":"Wising","year":"2005","journal-title":"Microb. Infect."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/j.1600-0463.2004.apm1121006.x","article-title":"Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans: Involvement of the cytolethal distending toxin","volume":"112","author":"Belibasakis","year":"2004","journal-title":"APMIS"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1128\/IAI.70.5.2665-2669.2002","article-title":"The cytolethal distending toxin of Haemophilus ducreyi inhibits endothelial cell proliferation","volume":"70","author":"Svensson","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/mpat.2000.0422","article-title":"The impact of Haemophilus ducreyi cytolethal distending toxin on cells involved in immune response","volume":"30","author":"Svensson","year":"2001","journal-title":"Microb. Pathog."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.micinf.2004.07.003","article-title":"Interactions of Haemophilus ducreyi and purified cytolethal distending toxin with human monocyte-derived dendritic cells, macrophages and CD4+ T cells","volume":"6","author":"Xu","year":"2004","journal-title":"Microb. Infect."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1600-0757.2009.00331.x","article-title":"Aggregatibacter (Actinobacillus) actinomycetemcomitans: A triple A* periodontopathogen?","volume":"54","author":"Henderson","year":"2010","journal-title":"Periodontol 2000"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1128\/IAI.73.1.342-351.2005","article-title":"The cytolethal distending toxin induces receptor activator of NF-kB ligand expression in human gingival fibroblasts and periodontal ligament cells","volume":"73","author":"Belibasakis","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1600-0463.2008.01017.x","article-title":"Cytolethal distending toxin upregulates RANKL expression in Jurkat T-cells","volume":"116","author":"Belibasakis","year":"2008","journal-title":"APMIS"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5925","DOI":"10.1128\/IAI.69.9.5925-5930.2001","article-title":"Recombinant Actinobacillus actinomycetemcomitans cytolethal distending toxin proteins are required to interact to inhibit human cell cycle progression and to stimulate human leukocyte cytokine synthesis","volume":"69","author":"Akifusa","year":"2001","journal-title":"Infect. Immun."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/3\/3\/172\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:55:28Z","timestamp":1760219728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/3\/3\/172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,7]]},"references-count":83,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2011,3]]}},"alternative-id":["toxins3030172"],"URL":"https:\/\/doi.org\/10.3390\/toxins3030172","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,7]]}}}