Special Issue "Cellular Interactions of the Cytolethal Distending Toxins"

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A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 April 2014)

Special Issue Editor

Guest Editor
Dr. Teresa Frisan

Department Cell and Molecular Biology (CMB), Berzelius väg 35, Box 285, S-171 77 Stockholm, Sweden
Website | E-Mail
Phone: (+46) 8 5248 6385
Interests: bacteria and cancer; host-microbe interaction; bacterial genotoxins; DNA damage response; carcinogenesis; bacteria and bacterial toxins internalization and intracellular trafficking

Special Issue Information

Dear Colleagues,

An emerging feature in commensal and pathogenic bacteria is the production of genotoxins, which are able to induce DNA damage in the target cells. The first family of bacterial genotoxins described is the cytolethal distending toxin (CDT). The discovery of this novel type of protein toxins has given a new perspective to the field of cellular microbiology, ranging from the characterization of the toxin internalization and intracellular trafficking, since this was the first bacterial protein toxin that needed to be translocated to the nuclear compartment, to the understanding of the chronic effects of cellular intoxication in term of acquisition of carcinogenic traits, such as genomic instability.

This special issue aims to provide the state of the art of several aspects of the CDTs biology, such as internalization and intracellular trafficking, cellular effects of intoxication in vitro, the consequences of acute and chronic infection with CDT-producing bacteria in in vivo models, as well as epidemiological studies linking CDT with specific diseases.

Dr. Teresa Frisan
Guest Editor


Submission

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Keywords

  • toxin internalization
  • intracellular trafficking
  • cellular responses
  • in vivo models
  • genotoxic stress

Published Papers (3 papers)

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Review

Open AccessReview The Cytolethal Distending Toxin Effects on Mammalian Cells: A DNA Damage Perspective
Cells 2014, 3(2), 592-615; doi:10.3390/cells3020592
Received: 16 April 2014 / Revised: 28 May 2014 / Accepted: 28 May 2014 / Published: 11 June 2014
Cited by 9 | PDF Full-text (1382 KB) | HTML Full-text | XML Full-text
Abstract
The cytolethal distending toxin (CDT) is produced by many pathogenic Gram-negative bacteria and is considered as a virulence factor. In human cells, CDT exposure leads to a unique cytotoxicity associated with a characteristic cell distension and induces a cell cycle arrest dependent on
[...] Read more.
The cytolethal distending toxin (CDT) is produced by many pathogenic Gram-negative bacteria and is considered as a virulence factor. In human cells, CDT exposure leads to a unique cytotoxicity associated with a characteristic cell distension and induces a cell cycle arrest dependent on the DNA damage response (DDR) triggered by DNA double-strand breaks (DSBs). CDT has thus been classified as a cyclomodulin and a genotoxin. Whereas unrepaired damage can lead to cell death, effective, but improper repair may be detrimental. Indeed, improper repair of DNA damage may allow cells to resume the cell cycle and induce genetic instability, a hallmark in cancer. In vivo, CDT has been shown to induce the development of dysplastic nodules and to lead to genetic instability, defining CDT as a potential carcinogen. It is therefore important to characterize the outcome of the CDT-induced DNA damage and the consequences for intoxicated cells and organisms. Here, we review the latest results regarding the host cell response to CDT intoxication and focus on DNA damage characteristics, cell cycle modulation and cell outcomes. Full article
(This article belongs to the Special Issue Cellular Interactions of the Cytolethal Distending Toxins)
Open AccessReview Breaking the Gingival Epithelial Barrier: Role of the Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin in Oral Infectious Disease
Cells 2014, 3(2), 476-499; doi:10.3390/cells3020476
Received: 17 April 2014 / Revised: 8 May 2014 / Accepted: 15 May 2014 / Published: 23 May 2014
Cited by 6 | PDF Full-text (3418 KB) | HTML Full-text | XML Full-text
Abstract
The Gram-negative bacterium Aggregatibacter actinomycetemcomitans is part of the HACEK group that causes infective endocarditis, a constituent of the oral flora that promotes some forms of periodontal disease and a member of the family of species that secrete a cytolethal distending toxin (Cdt).
[...] Read more.
The Gram-negative bacterium Aggregatibacter actinomycetemcomitans is part of the HACEK group that causes infective endocarditis, a constituent of the oral flora that promotes some forms of periodontal disease and a member of the family of species that secrete a cytolethal distending toxin (Cdt). The family of bacteria that express the cdt genes participate in diseases that involve the disruption of a mucosal or epithelial layer. In vitro studies have shown that human gingival epithelial cells (HGEC) are native targets of the Cdt that typically induces DNA damage that signals growth arrest at the G2/M interphase of the cell cycle. The gingival epithelium is an early line of defense in the oral cavity against microbial assault. When damaged, bacteria collectively gain entry into the underlying connective tissue where microbial products can affect processes and pathways in infiltrating inflammatory cells culminating in the destruction of the attachment apparatus of the tooth. One approach has been the use of an ex vivo gingival explant model to assess the effects of the Cdt on the morphology and integrity of the tissue. The goal of this review is to provide an overview of these studies and to critically examine the potential contribution of the Cdt to the breakdown of the protective gingival barrier. Full article
(This article belongs to the Special Issue Cellular Interactions of the Cytolethal Distending Toxins)
Open AccessReview Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins
Cells 2014, 3(2), 236-246; doi:10.3390/cells3020236
Received: 13 January 2014 / Revised: 18 March 2014 / Accepted: 24 March 2014 / Published: 4 April 2014
Cited by 5 | PDF Full-text (194 KB) | HTML Full-text | XML Full-text
Abstract
The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs
[...] Read more.
The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases. Full article
(This article belongs to the Special Issue Cellular Interactions of the Cytolethal Distending Toxins)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Review
Title: Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins
Authors: Georgios N. Belibasakis 1,* and Nagihan Bostanci 2
Affiliations: 1 Oral Microbiology and Immunology, Institute of Oral Biology, Center of Dental Medicine, University of Zürich, Plattenstrasse 11, 8032 Zürich, Switzerland; E-Mail: George.Belibasakis@zzm.uzh.ch; Tel.: +41-446-343-306; Fax: +41-446-343-310.
2 Oral Translational Research, Institute of Oral Biology, Center of Dental Medicine, University of Zürich, Plattenstrasse 11, 8032 Zürich, Switzerland; E-Mail: Nagihan.Bostanci@zzm.uzh.ch
Abstract: The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of unrelated to each other Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved. One special example is the induction of pathological bone destruction in the clinical condition of periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, attributed to its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.
Keywords: cytolethal distending toxin; cytokine; inflammation; bone remodeling; immune response; Aggregatibacter actinomycetemcomitans

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