Inhibition of epithelial cell apoptosis by Porphyromonas gingivalis

Nakhjiri, Simin F.

doi:10.1016/s0378-1097(01)00213-0

Cited by 75 publications

(124 citation statements)

References 15 publications

(32 reference statements)

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“…Hence, reduced protease expression will contribute to the long-term survival of the host cells. In support of this concept, epithelial cells infected with P. gingivalis do not undergo apoptosis [50] and can survive for up to eight days after infection [6]. Thus, intracellular P. gingivalis appear to be adapted for long-term survival and coexistence with the host, and may not be overtly pathogenic.…”

Section: Insights Into the Intracellular Lifestyle Of P Gingivalismentioning

confidence: 99%

Quantitative proteomics of intracellular Porphyromonas gingivalis

Xia¹,

Wang²,

Taub³

et al. 2007

Proteomics

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Whole-cell quantitative proteomic analyses were conducted to investigate the change from an extracellular to intracellular lifestyle for Porphyromonas gingivalis, a Gram-negative intracellular pathogen associated with periodontal disease. Global protein abundance data for P. gingivalis strain ATCC 33277 internalized for 18 hours within human gingival epithelial cells and controls exposed to gingival cell culture medium were obtained at sufficient coverage to provide strong evidence that these changes are profound. A total of 385 proteins were over-expressed in internalized P. gingivalis relative to controls; 240 proteins were shown to be under-expressed. This represented in total about 28% of the protein encoding ORFs annotated for this organism, and slightly less than half of the proteins that were observed experimentally. Production of several proteases, including the classical virulence factors RgpA, RgpB, and Kgp, was decreased. A separate validation study was carried out in which a 16-fold dilution of the P. gingivalis proteome was compared to the undiluted sample in order to assess the quantitative false negative rate (all ratios truly alternative). Truly null (no change) abundance ratios from technical replicates were used to assess the rate of quantitative false positives over the entire proteome. A global comparison between the direction of abundance change observed and previously published bioinformatic gene pair predictions for P. gingivalis will assist with future studies of P. gingivalis gene regulation and operon prediction.

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Section: Insights Into the Intracellular Lifestyle Of P Gingivalismentioning

confidence: 99%

Quantitative proteomics of intracellular Porphyromonas gingivalis

Xia¹,

Wang²,

Taub³

et al. 2007

Proteomics

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“…These observations support the notion that P. gingivalis is present in small numbers when compared with the total microbiota of the periodontal pockets (Kumar et al, 2006) and, as it remains in the intracellular environment, can multiply and spread to neighboring cells (Tribble and Lamont, 2010), obtaining not only a privileged position to modulate the immune response, causing a 'dysbiosis' between the host and the subgingival microbiota (Darveu et al, 2012), but also a location that allows P. gingivalis to escape from the host eliminating mechanisms and from mechanical periodontal treatment, perpetuating the chronicity of the periodontitis. Furthermore, the existence of overloaded cells supports the ability of the host cells to withstand an extensive P. gingivalis colonization without losing viability, due to the induction of antiapoptotic mechanisms by P. gingivalis as a survival strategy (Nakhjiri et al, 2001). We were unable to detect A. actinomycetemcomitans in our subgingival plaque samples.…”

Section: Discussionmentioning

confidence: 69%

Novel strategy to detect and locate periodontal pathogens: The PNA-FISH technique

Mendes

Rocha

Azevedo

et al. 2016

Microbiological Research

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Purpose: We aim to develop peptic nucleic acid (PNA) probes for the identification and localization of Aggregatibacter actinomycetemcomintans and Porphyromonas gingivalis in sub-gingival plaque and gingival biopsies by Fluorescence in situ Hybridization (FISH).Methods: A PNA probe was designed for each microorganism. The PNA-FISH method was optimized to allow simultaneous hybridization of both microorganisms with their probe (PNA-FISH multiplex). After being tested on representative strains of P. gingivalis and A. actinomycetemcomitans, the PNA-FISH method was then adapted to detect microorganisms in the subgingival plaque and gingival samples, collected from patients with severe periodontitis. Results:The best hybridization conditions were found to be 59 • C for 150 min for both probes (PgPNA1007 and AaPNA235). The in silico sensitivity and specificity was both 100% for PgPNA1007 probe and 100% and 99.9% for AaPNA235 probe, respectively. Results on clinical samples showed that the PNA-FISH method was able to detect and discriminate target bacteria in the mixed microbial population of the subgingival plaque and within periodontal tissues.Conclusion: This investigation presents a new highly accurate method for P. gingivalis and A. actino-mycetemcomitans detection and co-location in clinical samples, in just few hours. With this technique we were able to observe spatial distribution of these species within polymicrobial communities in the periodontal pockets and, for the first time with the FISH method, in the organized gingival tissue.2

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“…Caspase-dependent P. gingivalis-induced apoptosis: Because of the close proximity between oral pathogens and host cells in the gingiva, the interplay of P. gingivalis and the various cell types present in the gingival crevice has been under intense scrutiny. It is becoming increasingly clear that host cell responses to pathogenic bacteria can involve either elevated apoptosis or suppression of cell death (144). The body of evidence reveals that P. gingivalis-induced apoptosis is cell type-specific.…”

Section: Apoptosis Can Occur With and Without Caspase Involvementmentioning

confidence: 99%

“…In addition, it has been demonstrated that P. gingivalis LPS can prevent apoptosis of neutrophils derived from a human promyelocytic cell line, which may prolong an acute inflammatory response resulting in an increased potential for tissue destruction (140). Experimental results of Nakhjiri, et al, suggested that the first response to P. gingivalis infection in primary gingival epithelial cells was apoptosis; however, over time P. gingivalis initiated anti-apoptotic signaling via increased levels of Bcl-2 and decreased levels of Bax that canceled the cells' death response and was even able to promote cell survival in the presence of the apoptotic inducer camptothecin (144). Furthermore, inhibition of the PI3-K/Akt pathway abolished the P. gingivalis-induced protection from apoptosis (230).…”

Section: P Gingivalis-induced Resistance To Apoptosismentioning

confidence: 99%

“…There is overwhelming evidence that host cell responses to pathogenic bacteria can involve either apoptosis induction or suppression of cell death (144) and that host cells appear to be able to distinguish between infecting organisms and their components (237). Recently, it has been proposed that the possibly finite number of pathways that the pathogen may have evolved to modulate could be characteristic of the organism's genus (75).…”

Section: P Gingivalis-induced Resistance To Apoptosismentioning

confidence: 99%

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Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

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Porphyromonas gingivalis, a major periodontal pathogen, must acquire nutrients from host derived substrates, overcome oxidative stress and subvert the immune system. These activities can be coordinated via the gingipains which represent the most significant virulence factor produced by this organism. In the context of our contribution to this field, we will review the current understanding of gingipain biogenesis, glycosylation, and regulation, as well as discuss their role in oxidative stress resistance and apoptosis. We can postulate a model, in which gingipains may be part of the mechanism for P. gingivalis virulence. KeywordsPorphyromonas gingivalis; gingipains; apoptosis; caspase-independent apoptosis; oxidative stress; VimA; anoikis; N-cadherin; VE-cadherin; integrin β1; VimA; VimE; VimF; DNA repair; glycosylation; virulence; host cell survival; HRgpA; RgpB; Kgp; Review INTRODUCTIONP. gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease and other systemic diseases [reviewed in (43,103)]. The inflammatory nature of periodontal disease implies that innate host defense mechanisms play a vital role in limiting bacterial growth. During active infection including tissue invasion, toxic reactive oxygen metabolites (e.g. superoxides, hydrogen peroxide and hydroxyl radicals) are mostly generated by polymorphonuclear leukocytes and macrophages (27,29). In order to survive in the inflammatory environment of the periodontal pocket, the bacterium must not only obtain nutrients for growth, but also overcome oxidative stress and subvert the immune defense system. Coordinated regulation of these activities would be beneficial to the bacterium. While there is documented evidence of the response of P. gingivalis to environmental stimulus (56,117,126), one possible mechanism for coordination may occur via the gingipains produced by this bacterium. The presence of P. gingivalis in the periodontal pocket and the high levels of gingipain activity detected in gingival crevicular fluid could implicate a role for gingipains in the destruction of the highly vascular periodontal tissue. Protease-associated degradation of cell-cell adhesion proteins on epithelial and endothelial cells resulting in cell death will compromise tissue integrity and facilitate spreading of the bacterium. Furthermore, degradation of the immune response components will facilitate the survival of the organism. Together, these activities may also satisfy the nutritional requirements of the organism. Gingipain-dependent heme accumulation on the bacterium cell surface may also act as an "oxidative sink", thus, leading to protection against oxidative stress (191,193). We will discuss the role of the gingipains in the survival/pathogenicity of P. gingivalis and the unique vim (virulence modulating) locus that is involved in regulation of the gingipains. We will highlight some of our observations that are consistent with the hypothesis that the gingipain...

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Inhibition of epithelial cell apoptosis by Porphyromonas gingivalis

Cited by 75 publications

References 15 publications

Quantitative proteomics of intracellular Porphyromonas gingivalis

Quantitative proteomics of intracellular Porphyromonas gingivalis

Novel strategy to detect and locate periodontal pathogens: The PNA-FISH technique

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

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