Cytolethal distending toxins

Thelestam, Mónica

doi:10.1007/s10254-004-0030-8

Cited by 84 publications

(68 citation statements)

References 97 publications

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“…We identified the active subunit of Cytolethal Distending Toxin (CdtB) only in APE. The CdtB active subunit induces DNA double-strand breakage, leading to host cell cycle arrest in the G2/M phase [116]. This is preferable in the AIEC pathotype, presumably because pauses and irregularities in host cell cycle give the bacteria time to proliferate and colonize host cells.…”

Section: Discussionmentioning

confidence: 99%

Transport proteins promoting Escherichia coli pathogenesis

Tang

Saier

2014

Microbial Pathogenesis

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Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies.

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Section: Discussionmentioning

confidence: 99%

Transport proteins promoting Escherichia coli pathogenesis

Tang

Saier

2014

Microbial Pathogenesis

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“…CDTs generally function as complexes of three protein subunits, encoded by three contiguous genes ( cdtA , cdtB , cdtC ) in a single operon [13]. Consistent with the AB model of intracellular acting toxins [14], CdtB functions as the enzymatic A-subunit and possesses DNase I-like activity responsible for inducing DNA damage within the nuclei of intoxicated cells [15], [16].…”

Section: Introductionmentioning

confidence: 86%

Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry

et al. 2014

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Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.

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“…The cytolethal distending toxin family constitutes a group of highly potent toxins that are produced by several Gramnegative bacteria [12]. All of the CDTs are composed of three protein components, CdtA, B, and C, showing varying degrees of sequence homology between the different species [13].…”

Section: Introductionmentioning

confidence: 99%