The cytolethal distending toxin of Aggregatibacter actinomycetemcomitans inhibits macrophage phagocytosis and subverts cytokine production

Ando-Suguimoto, Ellen S.; Silva, Maike Paulino da; Kawamoto, Dione; Chen, Casey; DiRienzo, Joseph M.; Mayer, Márcia Pinto Alves

doi:10.1016/j.cyto.2013.12.014

Cited by 43 publications

(37 citation statements)

References 49 publications

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“…These cytokines induce the synthesis of cyclooxygenase-2, which in turn leads to the production of prostaglandins that alter hypothalamic temperature control, leading to an increase in heat production, the conservation of heat and finally fever [27]. Purified CDT from Aggregatibacter actinomycetemcomitans stimulated the production of IL-6, but not IL-1β or tumor necrosis factor alpha cytokines, in gingival fibroblasts [28], and increased IL-1β, IL-12 and IL-10 production in macrophages [29]. Future research should elucidate whether CDT from E. coli actually induces the production of endogenous pyrogens in humans.…”

Section: Discussionmentioning

confidence: 99%

Cytolethal distending toxin-producing Escherichia coli strains causing severe diarrhoea in young Mexican children

et al. 2017

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Introduction. Cytolethal distending toxins (CDTs), encoded by cdt genes, have DNase activity leading to cellular and nuclear distension, resulting in irreversible cell cycle arrest and apoptosis of target cells. cdt-positive Escherichia coli strains have been isolated from children with diarrhoea. There is, however, scant information on the prevalence and clinical presentation of diarrhoeal disease caused by these strains. Furthermore, toxin production of cdt-positive strains is rarely confirmed. We report five young children with diarrhoea caused by CDT-producing E. coli in whom stools were negative for other bacterial or enteric pathogens.Case presentation. On admission to hospital, all children presented watery diarrhoea with high stool output (range 7–20 stools/24 h); five had fever of 38 °C or more and four presented vomiting. Dehydration was present in four patients, one of whom had hypovolaemic shock; one child also presented hyponatraemia and hypokalaemia. In two children, cdt-positive strains were classified as typical and atypical enteropathogenic E. coli, and the remaining three harboured cdt-positive strains that did not belong to any diarrhoeagenic pathogroup. One cdt-positive strain from each case was characterized by a CDT cytotoxic assay and a cdt type-specific PCR. All strains produced the characteristic cellular intoxication due to CDT. Two strains carried the cdt-I, one cdt-III, one cdt-IV, and one concurrently had cdt-I, cdt-II and cdt-III genes.Conclusion. Our results suggest that CDT-producing E. coli strains are an infrequent, albeit significant, cause of severe diarrhoeal illness in children. Future research should measure the true burden of cdt-positive E. coli diarrhoea among children.

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Section: Discussionmentioning

confidence: 99%

Cytolethal distending toxin-producing Escherichia coli strains causing severe diarrhoea in young Mexican children

et al. 2017

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“…Therefore, by altering the barrier integrity of the gingival epithelium, CDT-producing bacteria may allow the access to the underlying connective tissue of the toxin and favor the invasion and colonization by the microbial components present in the oral mucosa, fueling the inflammatory process. The presence of the toxin within the connective tissue may further enhance inflammation, since it has been demonstrated that AactCDT in vitro promotes the secretion of a wide range of proinflammatory cytokines, such as IL-1β, IL-6, IL-8, and IFN-γ, IL-10, and IL-12 from PBMCs and the macrophage cell line Raw274.7 [194,195] and IL-6 from resident fibroblasts [196].…”

Section: Periodontitismentioning

confidence: 99%

Bacterial genotoxins

Frisan

2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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“…Nitric oxide production was altered in macrophage cultures due to the presence of the Aa Cdt [53]. Exposure of macrophages to the toxin also resulted in increased levels of IL-1β, IL-10, IL-20 and TNF-α.…”

Section: Aggregatibacter Actinomycetemcomitans Cdt Structure and Fmentioning

confidence: 99%

“…In addition, results of in vitro experiments with U937 cells, a macrophage-like cell line, suggested that macrophages are potential in vivo targets of the toxin [128]. The Aa Cdt may disrupt macrophages by inhibiting phagocytic activity, modulating nitric oxide production and altering the expression of pro-inflammatory and anti-inflammatory cytokines [53,129]. However, it should also be noted that A. actinomycetemcomitans resides in a biofilm external to the tissue and may be protected to some degree from immune surveillance and clearance by phagocytosis.…”

Section: Breakdown Of the Gingival Epithelial Barriermentioning

confidence: 99%

Breaking the Gingival Epithelial Barrier: Role of the Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin in Oral Infectious Disease

DiRienzo

2014

Cells

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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.

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The cytolethal distending toxin of Aggregatibacter actinomycetemcomitans inhibits macrophage phagocytosis and subverts cytokine production

Cited by 43 publications

References 49 publications

Cytolethal distending toxin-producing Escherichia coli strains causing severe diarrhoea in young Mexican children

Cytolethal distending toxin-producing Escherichia coli strains causing severe diarrhoea in young Mexican children

Bacterial genotoxins

Breaking the Gingival Epithelial Barrier: Role of the Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin in Oral Infectious Disease

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