Cytolethal Distending Toxin: A Unique Variation on the AB Toxin Paradigm

DiRienzo, Joseph M.

doi:10.1155/2014/249056

Cited by 6 publications

(4 citation statements)

References 213 publications

(321 reference statements)

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“…Cytholetal distending toxin (CDT) is produced by a variety of Gram-negative bacteria such as E. coli, Helicobacter hepaticus, Actinobacillus actinomycetemcomitans and other bacteria (DiRienzo, 2014 ; Taieb et al, 2016 ; Table 1 ). Initially CDT, a member of AB 2 toxin superfamily, was described in 1987 in a pathogenic E. coli strain isolated from a child (Anderson et al, 1987 ).…”

Section: Bacterial Cyclomodulinsmentioning

confidence: 99%

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Filho

Nicolas

Castro

et al. 2017

Front. Cell. Infect. Microbiol.

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Some bacterial pathogens modulate signaling pathways of eukaryotic cells in order to subvert the host response for their own benefit, leading to successful colonization and invasion. Pathogenic bacteria produce multiple compounds that generate favorable conditions to their survival and growth during infection in eukaryotic hosts. Many bacterial toxins can alter the cell cycle progression of host cells, impairing essential cellular functions and impeding host cell division. This review summarizes current knowledge regarding cyclomodulins, a heterogeneous family of bacterial effectors that induce eukaryotic cell cycle alterations. We discuss the mechanisms of actions of cyclomodulins according to their biochemical properties, providing examples of various cyclomodulins such as cycle inhibiting factor, γ-glutamyltranspeptidase, cytolethal distending toxins, shiga toxin, subtilase toxin, anthrax toxin, cholera toxin, adenylate cyclase toxins, vacuolating cytotoxin, cytotoxic necrotizing factor, Panton-Valentine leukocidin, phenol soluble modulins, and mycolactone. Special attention is paid to the benefit provided by cyclomodulins to bacteria during colonization of the host.

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Section: Bacterial Cyclomodulinsmentioning

confidence: 99%

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Filho

Nicolas

Castro

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Cdts are known to form a large subfamily of AB 2 toxins and spread throughout a variety of Gram-negative bacteria (reviewed in [ 157 ]). Amongst this extensive toxin family, there are five different Cdt variants known at the present day which are only found in E. coli .…”

Section: Toxins Of Lee-negative Stecmentioning

confidence: 99%

Toxins of Locus of Enterocyte Effacement-Negative Shiga Toxin-Producing Escherichia coli

Krause

Barth

Schmidt

2018

Toxins

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Studies on Shiga toxin-producing Escherichia coli (STEC) typically examine and classify the virulence gene profiles based on genomic analyses. Among the screened strains, a subgroup of STEC which lacks the locus of enterocyte effacement (LEE) has frequently been identified. This raises the question about the level of pathogenicity of such strains. This review focuses on the advantages and disadvantages of the standard screening procedures in virulence profiling and summarizes the current knowledge concerning the function and regulation of toxins encoded by LEE-negative STEC. Although LEE-negative STEC usually come across as food isolates, which rarely cause infections in humans, some serotypes have been implicated in human diseases. In particular, the LEE-negative E. coli O104:H4 German outbreak strain from 2011 and the Australian O113:H21 strain isolated from a HUS patient attracted attention. Moreover, the LEE-negative STEC O113:H21 strain TS18/08 that was isolated from minced meat is remarkable in that it not only encodes multiple toxins, but in fact expresses three different toxins simultaneously. Their characterization contributes to understanding the virulence of the LEE-negative STEC.

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“…The Cdt is the only AB toxin, identified to date, that traffics to the nucleus. Many of the other members of this toxin superfamily have a cytosolic target [ 1 ]. Translocation of CdtB to the nucleus in a variety of Cdt-sensitive cells seems to indicate that DNA nicking or cutting is the primary mode of action of the toxin.…”

Section: Steps In the Intoxication Processmentioning

confidence: 99%

“…Typical members of this subclass are produced by Gram-negative bacteria and those that are expressed from a complete cdt operon have an AB 2 subunit configuration. Representative examples include: Aggregatibacter actinomycetemcomitans ( Aa Cdt); Campylobacter jejuni ( Cj Cdt); Escherichia coli ( Ec ICdt, Ec IICdt, Ec IIICdt, Ec VCdt); Haemophilius ducreyi ( Hd Cdt); Helicobacter hepaticus ( Hh Cdt); Providencia alcalifaciens ( Pa Cdt); Shigella boydii ( Sb Cdt) and Shigella dysenteriae ( Sd Cdt) (reviewed in [ 1 ]). The A subunit, CdtB, is an enzyme, with an average molecular size of 29 kDa, that exhibits cation-dependent metalloenzyme activities, in vitro , characteristic of endonucleases [ 2 , 3 ], inositol polyphosphate 5-phosphatases [ 4 ] and sphingomelinases [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Uptake and Processing of the Cytolethal Distending Toxin by Mammalian Cells

DiRienzo

2014

Toxins

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The cytolethal distending toxin (Cdt) is a heterotrimeric holotoxin produced by a diverse group of Gram-negative pathogenic bacteria. The Cdts expressed by the members of this group comprise a subclass of the AB toxin superfamily. Some AB toxins have hijacked the retrograde transport pathway, carried out by the Golgi apparatus and endoplasmic reticulum (ER), to translocate to cytosolic targets. Those toxins have been used as tools to decipher the roles of the Golgi and ER in intracellular transport and to develop medically useful delivery reagents. In comparison to the other AB toxins, the Cdt exhibits unique properties, such as translocation to the nucleus, that present specific challenges in understanding the precise molecular details of the trafficking pathway in mammalian cells. The purpose of this review is to present current information about the mechanisms of uptake and translocation of the Cdt in relation to standard concepts of endocytosis and retrograde transport. Studies of the Cdt intoxication process to date have led to the discovery of new translocation pathways and components and most likely will continue to reveal unknown features about the mechanisms by which bacterial proteins target the mammalian cell nucleus. Insight gained from these studies has the potential to contribute to the development of novel therapeutic strategies.

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Cytolethal Distending Toxin: A Unique Variation on the AB Toxin Paradigm

Cited by 6 publications

References 213 publications

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Toxins of Locus of Enterocyte Effacement-Negative Shiga Toxin-Producing Escherichia coli

Uptake and Processing of the Cytolethal Distending Toxin by Mammalian Cells

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