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

DiRienzo, Joseph M.

doi:10.3390/cells3020476

Cited by 41 publications

(43 citation statements)

References 129 publications

(159 reference statements)

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“…Persistence of oral bacterial infection initiates a signaling cascade in immune cells and epithelial cells that activate systemic inflammatory processes known to promote carcinogenesis 27 , 28 . Certain oral bacterial species could also exert direct genotoxic effects or engage in molecular events that perturb host cellular survival and proliferation pathways 29 , 30 . In accordance with this view, F. nucleatum has been detected in colorectal tumors and was shown to have direct tumorigenic effects on colonic epithelial cells 10 , 11 .…”

Section: Discussionmentioning

confidence: 87%

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Mai

Genco

LaMonte

et al. 2016

Journal of Periodontology

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Background Extraoral translocation of oral bacteria may contribute to associations between periodontal disease and cancer. The associations among the presence of three orange-complex periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus), two red-complex periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia), and cancer risk were investigated. Methods A total of 1,252 postmenopausal females enrolled in the Buffalo Osteoporosis and Periodontal Disease Study were followed prospectively. Baseline subgingival plaque samples were assessed for the presence of periodontal pathogens using indirect immunofluorescence. Incident cancer cases were adjudicated by staff physicians via review of medical records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of periodontal pathogens with total cancer and site-specific cancer risk in unadjusted and multivariable-adjusted models. Results Neither the presence of individual pathogens nor the presence of any red-complex pathogens was associated with total cancer or site-specific cancers. Borderline associations were seen among the presence of any orange-complex pathogens (F. nucleatum, P. intermedia, and C. rectus), total cancer risk (HR = 1.35, 95% CI = 1.00 to 1.84), and lung cancer risk (HR = 3.02, 95% CI = 0.98 to 9.29). Conclusions No associations were found between the presence of individual subgingival pathogens and cancer risk. However, there were suggestions of borderline positive associations of the presence of any orange-complex pathogens with total cancer and lung cancer risk. The study is limited by the small number of cancer cases and the assessment of only five oral bacteria. Additional research is needed to understand the possi ble role of periodontal disease in carcinogenesis.

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Section: Discussionmentioning

confidence: 87%

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Mai

Genco

LaMonte

et al. 2016

Journal of Periodontology

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“…This lack of effect on A . actinomycetemcomitans may be related to deeper initial probing depth (> 6.00 mm) and/or deep penetration of the microbe into the pocket soft‐tissue wall .…”

Section: Diode Lasers and The Treatment Of Periodontitismentioning

confidence: 99%

“…P. gingivalis, Tannerella forsythia and Treponema denticola) following treatment with scaling and root planing + 980 nm diode but no treatment modality reduced the levels of A. actinomycetemcomitans. This lack of effect on A. actinomycetemcomitans may be related to deeper initial probing depth (> 6.00 mm) and/or deep penetration of the microbe into the pocket soft-tissue wall (97,177).…”

Section: Diode Lasers and The Treatment Of Periodontitismentioning

confidence: 99%

Lasers and the treatment of periodontitis: the essence and the noise

Cobb¹

2017

Periodontology 2000

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The dental literature contains 25 years of accumulated reports and clinical studies addressing the utility of lasers in the treatment of periodontitis, both as a monotherapy or as an adjunct to surgical and nonsurgical therapy. Yet, the evidence from the 118 human clinical studies cited in this narrative review remains conflicted and insufficient to suggest that integration of a laser in a periodontal treatment protocol will provide antimicrobial and healing outcomes superior to those achieved by traditional therapy. When viewed as a collective body of evidence, it becomes apparent that a majority of the studies are underpowered and exhibit significant heterogeneity in design. Furthermore, the collected studies report a varied choice of parameters, even within the same wavelength of laser. There is little uniformity between studies in the reporting of measured clinical parameters. Most studies reported 3- and/or 6-month post-treatment results; however, the range of time intervals includes studies reporting results from 1 week to up to 1-12 months or longer. Lastly, many studies were considered at risk for bias as a result of a lack of examiner masking and/or calibration. There is great need for well-designed, highly controlled multicenter clinical trials that are adequately powered in terms of subject enrollment, that use similar protocols in terms of laser parameters and that report measureable outcomes in a uniform manner. Without such studies, the questions surrounding the use of lasers in the treatment of periodontal disease will persist.

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“…In addition to forming a protective biofilm, A. actinomycetemcomitans has many virulence factors, including secreted toxins, such as leukotoxin and cytolethal distending toxin (for reviews, see refs [13,14]. ), which harm host tissues and defense systems.…”

Section: Introductionmentioning

confidence: 99%

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

et al. 2018

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Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43 nM in static settings and 2.4 μM in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested β-lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.

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

Cited by 41 publications

References 129 publications

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study

Lasers and the treatment of periodontitis: the essence and the noise

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

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