The Biology of the Cytolethal Distending Toxins
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 surfac...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2011-03-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/3/3/172/ |
| _version_ | 1798006786879389696 |
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| author | Teresa Frisan Ximena Cortes-Bratti Riccardo Guidi Lina Guerra |
| author_facet | Teresa Frisan Ximena Cortes-Bratti Riccardo Guidi Lina Guerra |
| author_sort | Teresa Frisan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:00:06Z |
| format | Article |
| id | doaj.art-12ecaf587f3040c3ad91516a89bee627 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T13:00:06Z |
| publishDate | 2011-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-12ecaf587f3040c3ad91516a89bee6272022-12-22T04:22:57ZengMDPI AGToxins2072-66512011-03-013317219010.3390/toxins3030172The Biology of the Cytolethal Distending ToxinsTeresa FrisanXimena Cortes-BrattiRiccardo GuidiLina GuerraThe 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.http://www.mdpi.com/2072-6651/3/3/172/cytolethal distending toxinbacterial genotoxintoxin internalizationDNA damageDNA damage responsesurvival signalsvirulence factorchancroidperiodontitiscolitis/hepatitis |
| spellingShingle | Teresa Frisan Ximena Cortes-Bratti Riccardo Guidi Lina Guerra The Biology of the Cytolethal Distending Toxins Toxins cytolethal distending toxin bacterial genotoxin toxin internalization DNA damage DNA damage response survival signals virulence factor chancroid periodontitis colitis/hepatitis |
| title | The Biology of the Cytolethal Distending Toxins |
| title_full | The Biology of the Cytolethal Distending Toxins |
| title_fullStr | The Biology of the Cytolethal Distending Toxins |
| title_full_unstemmed | The Biology of the Cytolethal Distending Toxins |
| title_short | The Biology of the Cytolethal Distending Toxins |
| title_sort | biology of the cytolethal distending toxins |
| topic | cytolethal distending toxin bacterial genotoxin toxin internalization DNA damage DNA damage response survival signals virulence factor chancroid periodontitis colitis/hepatitis |
| url | http://www.mdpi.com/2072-6651/3/3/172/ |
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