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Ashu Sharma - One of the best experts on this subject based on the ideXlab platform.
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persistence of tannerella Forsythia and fusobacterium nucleatum in dental plaque a strategic alliance
Current Oral Health Reports, 2020Co-Authors: Ashu SharmaAbstract:The Gram-negative oral pathogen Tannerella Forsythia is implicated in the pathogenesis of periodontitis, an inflammatory disease characterized by progressive destruction of the tooth-supporting structures affecting over 700 million people worldwide. This review highlights the basis of why and how T. Forsythia interacts with Fusobacterium nucleatum, a bacterium considered to be a bridge between the early and late colonizing bacteria of the dental plaque. The recent findings indicate that these two organisms have a strong mutualistic relationship that involves foraging by T. Forsythia on F. nucleatum peptidoglycan and utilization of glucose, released by the hydrolytic activity of T. Forsythia glucanase, as a nutrient by F. nucleatum. In addition, T. Forsythia has the unique ability to generate a toxic and inflammogenic compound, methylglyoxal, from glucose. This compound can induce inflammation, leading to the degradation of periodontal tissues and release of host components as nutrients for bacteria to further exacerbate the disease. In summary, this article will present our current understanding of mechanisms underpinning T. Forsythia-F. nucleatum mutualism, and how this mutualism might impact periodontal disease progression.
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Persistence of Tannerella Forsythia and Fusobacterium nucleatum in Dental Plaque: a Strategic Alliance
Current Oral Health Reports, 2020Co-Authors: Ashu SharmaAbstract:Purpose of Review The Gram-negative oral pathogen Tannerella Forsythia is implicated in the pathogenesis of periodontitis, an inflammatory disease characterized by progressive destruction of the tooth-supporting structures affecting over 700 million people worldwide. This review highlights the basis of why and how T. Forsythia interacts with Fusobacterium nucleatum , a bacterium considered to be a bridge between the early and late colonizing bacteria of the dental plaque. Recent Findings The recent findings indicate that these two organisms have a strong mutualistic relationship that involves foraging by T. Forsythia on F. nucleatum peptidoglycan and utilization of glucose, released by the hydrolytic activity of T. Forsythia glucanase, as a nutrient by F. nucleatum . In addition, T. Forsythia has the unique ability to generate a toxic and inflammogenic compound, methylglyoxal, from glucose. This compound can induce inflammation, leading to the degradation of periodontal tissues and release of host components as nutrients for bacteria to further exacerbate the disease. Summary In summary, this article will present our current understanding of mechanisms underpinning T. Forsythia - F. nucleatum mutualism, and how this mutualism might impact periodontal disease progression.
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tannerella Forsythia produced methylglyoxal causes accumulation of advanced glycation endproducts to trigger cytokine secretion in human monocytes
Molecular Oral Microbiology, 2018Co-Authors: Rajendra P Settem, Kiyonobu Honma, Mira Shankar, Miaomiao Li, Michael J Lamonte, Ding Xu, Robert J Genco, Richard W Browne, Ashu SharmaAbstract:: The periodontal pathogen Tannerella Forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival-crevicular fluid are increased and are correlated with the T. Forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. Forsythia. While wild-type T.Forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. Forsythia parental strain, the spent medium of the T. Forsythia mgsA-deletion strain induced significantly lower nuclear factor-kappa B activity as well as proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The ability of T. Forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis-based collagen chain mobility shift assay. Together these data demonstrated that T. Forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.
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β glucanase activity of the oral bacterium tannerella Forsythia contributes to the growth of a partner species fusobacterium nucleatum in cobiofilms
Applied and Environmental Microbiology, 2017Co-Authors: Kiyonobu Honma, Angela Ruscitto, Ashu SharmaAbstract:ABSTRACT Tannerella Forsythia and Fusobacterium nucleatum are dental plaque bacteria implicated in the development of periodontitis. These two species have been shown to form synergistic biofilms and have been found to be closely associated in dental plaque biofilms. A number of genetic loci for TonB-dependent membrane receptors (TDR) for glycan acquisition, with many existing in association with genes coding for enzymes involved in the breakdown of complex glycans, have been identified in T. Forsythia. In this study, we focused on a locus, BFO_0186-BFO_0188, that codes for a predicted TDR-SusD transporter along with a putative β-glucan hydrolyzing enzyme (BFO_0186). This operon is located immediately downstream of a 2-gene operon that codes for a putative stress-responsive extracytoplasmic function (ECF) sigma factor and an anti-sigma factor. Here, we show that BFO_0186 expresses a β-glucanase that cleaves glucans with β-1,6 and β-1,3 linkages. Furthermore, the BFO_0186-BFO_0188 locus is upregulated, with an induction of β-glucanase activity, in cobiofilms of T. Forsythia and F. nucleatum. The β-glucanase activity in mixed biofilms in turn leads to an enhanced hydrolysis of β-glucans and release of glucose monomers and oligomers as nutrients for F. nucleatum. In summary, our study highlights the role of T. Forsythia β-glucanase expressed by the asaccharolytic oral bacterium T. Forsythia in the development of T. Forsythia-F. nucleatum mixed species biofilms, and suggest that dietary β-glucans might contribute in plaque development and periodontal disease pathogenesis. IMPORTANCE The development of dental plaque biofilm is a complex process in which metabolic, chemical and physical interactions between bacteria take a central role. Previous studies have shown that the dental pathogens T. Forsythia and F. nucleatum form synergistic biofilms and are closely associated in human dental plaque. In this study, we show that β-glucanase from the periodontal pathogen T. Forsythia plays a role in the formation of T. Forsythia-F. nucleatum cobiofilms by hydrolyzing β-glucans to glucose as a nutrient. We also unveiled that the expression of T. Forsythia β-glucanase is induced in response to F. nucleatum sensing. This study highlights the involvement of β-glucanase activity in the development of T. Forsythia-F. nucleatum biofilms and suggests that intake of dietary β-glucans might be a contributing risk factor in plaque development and periodontal disease pathogenesis.
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macrophage inducible c type lectin mincle recognizes glycosylated surface s layer of the periodontal pathogen tannerella Forsythia
PLOS ONE, 2017Co-Authors: Sreedevi Chinthamani, Rajendra P Settem, Kiyonobu Honma, Ashu SharmaAbstract:: The oral pathogen Tannerella Forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. T. Forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. The T. Forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. In this study, we aimed to determine if Mincle might be involved in the recognition of T. Forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. Forsythia S-layer. Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. Forsythia as well as its S-layer. Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. Forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium.
Bongkyu Choi - One of the best experts on this subject based on the ideXlab platform.
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regulation of il 24 in human oral keratinocytes stimulated with tannerella Forsythia
Molecular Oral Microbiology, 2019Co-Authors: Yeonkyeong Ko, Sunjin An, Bongkyu ChoiAbstract:: Interleukin-24 is a pleiotropic immunoregulatory cytokine and a member of the IL-20R subfamily of the IL-10 family. The aim of this study was to investigate the regulation of IL-24 in the human oral keratinocyte cell line HOK-16B following infection with Tannerella Forsythia, a major periodontal pathogen. T. Forsythia induced the expression of IL-24 mRNA and the secretion of glycosylated IL-24 in HOK-16B cells. Glycosylation of IL-24 is linked to its solubility and bioavailability. T. Forsythia-stimulated reactive oxygen species (ROS) induced the expression of IL-24, which was regulated by IL-6. The ROS inhibitor N-acetylcysteine and MAPK inhibitors significantly reduced the expression of IL-6 and IL-24 induced by T. Forsythia. Recombinant human IL-24 significantly enhanced the expression of IL-1α, IL-8, CXCL10, and MCP-1 in HOK-16B cells. Together, these results indicate that ROS, MAPKs, and IL-6 comprise the axis of IL-24 expression in HOK-16B cells stimulated with T. Forsythia. Thus, IL-24 may be involved in inflammation in oral keratinocytes.
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Regulation of IL‐24 in human oral keratinocytes stimulated with Tannerella Forsythia
Molecular Oral Microbiology, 2019Co-Authors: Yeon‐kyeong Ko, Sun‐jin An, Bongkyu ChoiAbstract:: Interleukin-24 is a pleiotropic immunoregulatory cytokine and a member of the IL-20R subfamily of the IL-10 family. The aim of this study was to investigate the regulation of IL-24 in the human oral keratinocyte cell line HOK-16B following infection with Tannerella Forsythia, a major periodontal pathogen. T. Forsythia induced the expression of IL-24 mRNA and the secretion of glycosylated IL-24 in HOK-16B cells. Glycosylation of IL-24 is linked to its solubility and bioavailability. T. Forsythia-stimulated reactive oxygen species (ROS) induced the expression of IL-24, which was regulated by IL-6. The ROS inhibitor N-acetylcysteine and MAPK inhibitors significantly reduced the expression of IL-6 and IL-24 induced by T. Forsythia. Recombinant human IL-24 significantly enhanced the expression of IL-1α, IL-8, CXCL10, and MCP-1 in HOK-16B cells. Together, these results indicate that ROS, MAPKs, and IL-6 comprise the axis of IL-24 expression in HOK-16B cells stimulated with T. Forsythia. Thus, IL-24 may be involved in inflammation in oral keratinocytes.
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tannerella Forsythia groel induces inflammatory bone resorption and synergizes with interleukin 17
Molecular Oral Microbiology, 2017Co-Authors: Youngjung Jung, Yujung Choi, Sunjin An, Bongkyu ChoiAbstract:Summary Tannerella Forsythia is a major periodontal pathogen, and T. Forsythia GroEL is a molecular chaperone homologous to human heat shock protein 60. Interleukin (IL)-17 has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. Forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. Forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. Forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase (COX)-2 and concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. Forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. Forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. T. Forsythia GroEL induced IL-6, IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. T. Forsythia GroEL and IL-17 synergistically increased PGE2 production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. Forsythia GroEL injection, and simultaneous injection of T. Forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. Forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. Forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption. This article is protected by copyright. All rights reserved.
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gingipain dependent augmentation by porphyromonas gingivalis of phagocytosis of tannerella Forsythia
Molecular Oral Microbiology, 2016Co-Authors: Youngjung Jung, Bongkyu ChoiAbstract:: In the pathogenesis of periodontitis, Porphyromonas gingivalis plays a role as a keystone pathogen that manipulates host immune responses leading to dysbiotic oral microbial communities. Arg-gingipains (RgpA and RgpB) and Lys-gingipain (Kgp) are responsible for the majority of bacterial proteolytic activity and play essential roles in bacterial virulence. Therefore, gingipains are often considered as therapeutic targets. This study investigated the role of gingipains in the modulation by P. gingivalis of phagocytosis of Tannerella Forsythia by macrophages. Phagocytosis of T. Forsythia was significantly enhanced by coinfection with P. gingivalis in a multiplicity of infection-dependent and gingipain-dependent manner. Mutation of either Kgp or Rgp in the coinfecting P. gingivalis resulted in attenuated enhancement of T. Forsythia phagocytosis. Inhibition of coaggregation between the two bacterial species reduced phagocytosis of T. Forsythia in mixed infection, and this coaggregation was dependent on gingipains. Inhibition of gingipain protease activities in coinfecting P. gingivalis abated the coaggregation and the enhancement of T. Forsythia phagocytosis. However, the direct effect of protease activities of gingipains on T. Forsythia seemed to be minimal. Although most of the phagocytosed T. Forsythia were cleared in infected macrophages, more T. Forsythia remained in cells coinfected with gingipain-expressing P. gingivalis than in cells coinfected with the gingipain-null mutant or infected only with T. Forsythia at 24 and 48 h post-infection. Collectively, these results suggest that P. gingivalis, mainly via its gingipains, alters the clearance of T. Forsythia, and provide some insights into the role of P. gingivalis as a keystone pathogen.
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Tannerella Forsythia GroEL induces inflammatory bone resorption and synergizes with interleukin-17.
Molecular oral microbiology, 2016Co-Authors: Youngjung Jung, Yujung Choi, Hae-ri Lee, Hye-kyoung Jun, Bongkyu ChoiAbstract:Tannerella Forsythia is a major periodontal pathogen, and T. Forsythia GroEL is a molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL-17) has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. Forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. Forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. Forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2 ) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. Forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. Forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. Tannerella Forsythia GroEL induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. Both T. Forsythia GroEL and IL-17 synergistically increased PGE2 production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. Forsythia GroEL injection, and simultaneous injection of T. Forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. Forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. Forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption.
Christina Schäffer - One of the best experts on this subject based on the ideXlab platform.
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comparative genome characterization of the periodontal pathogen tannerella Forsythia
BMC Genomics, 2020Co-Authors: Nikolaus F Zwickl, Juliane C Dohm, Christina Schäffer, Nancy Stralispavese, Heinz HimmelbauerAbstract:Tannerella Forsythia is a bacterial pathogen implicated in periodontal disease. Numerous virulence-associated T. Forsythia genes have been described, however, it is necessary to expand the knowledge on T. Forsythia’s genome structure and genetic repertoire to further elucidate its role within pathogenesis. Tannerella sp. BU063, a putative periodontal health-associated sister taxon and closest known relative to T. Forsythia is available for comparative analyses. In the past, strain confusion involving the T. Forsythia reference type strain ATCC 43037 led to discrepancies between results obtained from in silico analyses and wet-lab experimentation. We generated a substantially improved genome assembly of T. Forsythia ATCC 43037 covering 99% of the genome in three sequences. Using annotated genomes of ten Tannerella strains we established a soft core genome encompassing 2108 genes, based on orthologs present in > = 80% of the strains analysed. We used a set of known and hypothetical virulence factors for comparisons in pathogenic strains and the putative periodontal health-associated isolate Tannerella sp. BU063 to identify candidate genes promoting T. Forsythia’s pathogenesis. Searching for pathogenicity islands we detected 38 candidate regions in the T. Forsythia genome. Only four of these regions corresponded to previously described pathogenicity islands. While the general protein O-glycosylation gene cluster of T. Forsythia ATCC 43037 has been described previously, genes required for the initiation of glycan synthesis are yet to be discovered. We found six putative glycosylation loci which were only partially conserved in other bacteria. Lastly, we performed a comparative analysis of translational bias in T. Forsythia and Tannerella sp. BU063 and detected highly biased genes. We provide resources and important information on the genomes of Tannerella strains. Comparative analyses enabled us to assess the suitability of T. Forsythia virulence factors as therapeutic targets and to suggest novel putative virulence factors. Further, we report on gene loci that should be addressed in the context of elucidating T. Forsythia’s protein O-glycosylation pathway. In summary, our work paves the way for further molecular dissection of T. Forsythia biology in general and virulence of this species in particular.
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Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella Forsythia strains and their cell surface mutants
Molecular Oral Microbiology, 2018Co-Authors: Susanne Bloch, Åsa Sjöling, Georgios N. Belibasakis, Nagihan Bostanci, Stephanie Zwicker, Elisabeth A Bostrom, Christina SchäfferAbstract:The oral pathogen Tannerella Forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. Forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. Forsythia strains ATCC 43037 and UB4 displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. Forsythia, monocytes secrete proinflammatory cytokines, chemokines and vascular endothelial growth factor (VEGF) with the release of interleukin-1β (IL-1β) and IL-7 being differentially regulated by the two T. Forsythia wild-type strains. Truncation of the bacteria's O-glycan leads to significant reduction of IL-1β and regulates macrophage inflammatory protein-1. HOK infected with T. Forsythia produce IL-1Ra, chemokines and VEGF. Although the two wild-type strains elicit preferential immune responses for IL-8, both truncation of the O-glycan and deletion of the S-layer result in significantly increased release of IL-8, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. Forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. Forsythia S-layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and hence play a pivotal role in orchestrating the bacterium's virulence.
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behavior of two tannerella Forsythia strains and their cell surface mutants in multispecies oral biofilms
Molecular Oral Microbiology, 2017Co-Authors: Susanne Bloch, Thomas Thurnheer, Georgios N. Belibasakis, Yukitaka Murakami, Christina SchäfferAbstract:As a member of subgingival multispecies biofilms, Tannerella Forsythia is commonly associated with periodontitis. The bacterium has a characteristic cell surface (S-) layer modified with a unique O-glycan. Both the S-layer and the O-glycan were analyzed in this study for their role in biofilm formation by employing an in vitro multispecies biofilm model mimicking the situation in the oral cavity. Different T. Forsythia strains and mutants with characterized defects in cell surface composition were incorporated into the model, together with nine species of select oral bacteria. The influence of the T. Forsythia S-layer and attached glycan on the bacterial composition of the biofilms was analyzed quantitatively using colony forming unit counts and quantitative real-time PCR, as well as qualitatively by fluorescence in situ hybridization and confocal laser scanning microscopy. This revealed that changes of the T. Forsythia cell surface did not affect the quantitative composition of the multispecies consortium, with the exception of Campylobacter rectus cell numbers. The localization of T. Forsythia within the bacterial agglomeration varied depending on changes in the S-layer glycan, and this also affected its aggregation with Porphyromonas gingivalis. This suggests a selective role for the glycosylated T. Forsythia S-layer in the positioning of this species within the biofilm, its co-localization with P. gingivalis, and the prevalence of C. rectus. These findings might translate into a potential role of T. Forsythia cell surface structures in the virulence of this species when interacting with host tissues and immune system, from within or beyond the biofilm. This article is protected by copyright. All rights reserved.
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Biofilm behavior of Tannerella Forsythia strains and S-layer glycosylation mutants
Journal of Oral Microbiology, 2017Co-Authors: Susanne Bloch, Thomas Thurnheer, Georgios N. Belibasakis, Yukitaka Murakami, Christina SchäfferAbstract:The periodontopathogen Tannerella Forsythia has a characteristic cell surface (S-) layer modified with a unique O-glycan. This structure was analyzed for its role in biofilm formation employing an in vitro multispecies biofilm model, into which different T. Forsythia strains and mutants with a modified cell surface composition were incorporated together with nine other oral species. The influence of the glycosylated T. Forsythia S-layer on the bacterial composition of the biofilms was analyzed quantitatively using quantitative real-time PCR as well as qualitatively by fluorescence in situ hybridization and confocal laser scanning microscopy. It was evident that while changes of the T. Forsythia cell surface did not affect the quantitative composition of the multispecies consortium, with the exception of Campylobacter rectus cell numbers, the localization of T. Forsythia within the biofilm and its aggregation with Porphyromonas gingivalis were changed. Thus, the glycosylated T. Forsythia S-layer might have relevance for positioning of this species within the biofilm and influence its co-localization with P. gingivalis and the prevalence of C. rectus. This might further pinpoint a pivotal role of T. Forsythia cell surface structures in the virulence of this species when interacting with host tissues and immune system, from within or beyond the biofilm.
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potential of the tannerella Forsythia s layer to delay the immune response
Journal of Dental Research, 2011Co-Authors: Gerhard Sekot, Gerald Posch, Oleh Andrukhov, Paul Messner, Xiaohui Rauschfan, Michael Matejka, Christina SchäfferAbstract:The periodontal pathogen Tannerella Forsythia possesses a glycosylated S-layer as an outermost cell decoration. While the S-layer provides a selection advantage to the bacterium in the natural habitat, its virulence potential remains to be investigated. In the present study, the immune responses of human macrophages and gingival fibroblasts upon stimulation with wild-type T. Forsythia and an S-layer-deficient mutant were investigated. The mRNA expression levels of the pro-inflammatory mediators IL-1β, TNF-α, and IL-8 were analyzed by qPCR, and the production of the corresponding cytokines was investigated by ELISA. The S-layer-deficient T. Forsythia mutant induced significantly higher levels of pro-inflammatory mediators compared with wild-type T. Forsythia, especially at the early phase of response. Analysis of these data suggests that the S-layer of T. Forsythia is an important virulence factor that attenuates the host immune response to this pathogen by evading the bacterium’s recognition by the innate...
Susanne Bloch - One of the best experts on this subject based on the ideXlab platform.
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Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella Forsythia strains and their cell surface mutants
Molecular Oral Microbiology, 2018Co-Authors: Susanne Bloch, Åsa Sjöling, Georgios N. Belibasakis, Nagihan Bostanci, Stephanie Zwicker, Elisabeth A Bostrom, Christina SchäfferAbstract:The oral pathogen Tannerella Forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. Forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. Forsythia strains ATCC 43037 and UB4 displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. Forsythia, monocytes secrete proinflammatory cytokines, chemokines and vascular endothelial growth factor (VEGF) with the release of interleukin-1β (IL-1β) and IL-7 being differentially regulated by the two T. Forsythia wild-type strains. Truncation of the bacteria's O-glycan leads to significant reduction of IL-1β and regulates macrophage inflammatory protein-1. HOK infected with T. Forsythia produce IL-1Ra, chemokines and VEGF. Although the two wild-type strains elicit preferential immune responses for IL-8, both truncation of the O-glycan and deletion of the S-layer result in significantly increased release of IL-8, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. Forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. Forsythia S-layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and hence play a pivotal role in orchestrating the bacterium's virulence.
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behavior of two tannerella Forsythia strains and their cell surface mutants in multispecies oral biofilms
Molecular Oral Microbiology, 2017Co-Authors: Susanne Bloch, Thomas Thurnheer, Georgios N. Belibasakis, Yukitaka Murakami, Christina SchäfferAbstract:As a member of subgingival multispecies biofilms, Tannerella Forsythia is commonly associated with periodontitis. The bacterium has a characteristic cell surface (S-) layer modified with a unique O-glycan. Both the S-layer and the O-glycan were analyzed in this study for their role in biofilm formation by employing an in vitro multispecies biofilm model mimicking the situation in the oral cavity. Different T. Forsythia strains and mutants with characterized defects in cell surface composition were incorporated into the model, together with nine species of select oral bacteria. The influence of the T. Forsythia S-layer and attached glycan on the bacterial composition of the biofilms was analyzed quantitatively using colony forming unit counts and quantitative real-time PCR, as well as qualitatively by fluorescence in situ hybridization and confocal laser scanning microscopy. This revealed that changes of the T. Forsythia cell surface did not affect the quantitative composition of the multispecies consortium, with the exception of Campylobacter rectus cell numbers. The localization of T. Forsythia within the bacterial agglomeration varied depending on changes in the S-layer glycan, and this also affected its aggregation with Porphyromonas gingivalis. This suggests a selective role for the glycosylated T. Forsythia S-layer in the positioning of this species within the biofilm, its co-localization with P. gingivalis, and the prevalence of C. rectus. These findings might translate into a potential role of T. Forsythia cell surface structures in the virulence of this species when interacting with host tissues and immune system, from within or beyond the biofilm. This article is protected by copyright. All rights reserved.
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Biofilm behavior of Tannerella Forsythia strains and S-layer glycosylation mutants
Journal of Oral Microbiology, 2017Co-Authors: Susanne Bloch, Thomas Thurnheer, Georgios N. Belibasakis, Yukitaka Murakami, Christina SchäfferAbstract:The periodontopathogen Tannerella Forsythia has a characteristic cell surface (S-) layer modified with a unique O-glycan. This structure was analyzed for its role in biofilm formation employing an in vitro multispecies biofilm model, into which different T. Forsythia strains and mutants with a modified cell surface composition were incorporated together with nine other oral species. The influence of the glycosylated T. Forsythia S-layer on the bacterial composition of the biofilms was analyzed quantitatively using quantitative real-time PCR as well as qualitatively by fluorescence in situ hybridization and confocal laser scanning microscopy. It was evident that while changes of the T. Forsythia cell surface did not affect the quantitative composition of the multispecies consortium, with the exception of Campylobacter rectus cell numbers, the localization of T. Forsythia within the biofilm and its aggregation with Porphyromonas gingivalis were changed. Thus, the glycosylated T. Forsythia S-layer might have relevance for positioning of this species within the biofilm and influence its co-localization with P. gingivalis and the prevalence of C. rectus. This might further pinpoint a pivotal role of T. Forsythia cell surface structures in the virulence of this species when interacting with host tissues and immune system, from within or beyond the biofilm.
Youngjung Jung - One of the best experts on this subject based on the ideXlab platform.
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tannerella Forsythia groel induces inflammatory bone resorption and synergizes with interleukin 17
Molecular Oral Microbiology, 2017Co-Authors: Youngjung Jung, Yujung Choi, Sunjin An, Bongkyu ChoiAbstract:Summary Tannerella Forsythia is a major periodontal pathogen, and T. Forsythia GroEL is a molecular chaperone homologous to human heat shock protein 60. Interleukin (IL)-17 has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. Forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. Forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. Forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase (COX)-2 and concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. Forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. Forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. T. Forsythia GroEL induced IL-6, IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. T. Forsythia GroEL and IL-17 synergistically increased PGE2 production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. Forsythia GroEL injection, and simultaneous injection of T. Forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. Forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. Forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption. This article is protected by copyright. All rights reserved.
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gingipain dependent augmentation by porphyromonas gingivalis of phagocytosis of tannerella Forsythia
Molecular Oral Microbiology, 2016Co-Authors: Youngjung Jung, Bongkyu ChoiAbstract:: In the pathogenesis of periodontitis, Porphyromonas gingivalis plays a role as a keystone pathogen that manipulates host immune responses leading to dysbiotic oral microbial communities. Arg-gingipains (RgpA and RgpB) and Lys-gingipain (Kgp) are responsible for the majority of bacterial proteolytic activity and play essential roles in bacterial virulence. Therefore, gingipains are often considered as therapeutic targets. This study investigated the role of gingipains in the modulation by P. gingivalis of phagocytosis of Tannerella Forsythia by macrophages. Phagocytosis of T. Forsythia was significantly enhanced by coinfection with P. gingivalis in a multiplicity of infection-dependent and gingipain-dependent manner. Mutation of either Kgp or Rgp in the coinfecting P. gingivalis resulted in attenuated enhancement of T. Forsythia phagocytosis. Inhibition of coaggregation between the two bacterial species reduced phagocytosis of T. Forsythia in mixed infection, and this coaggregation was dependent on gingipains. Inhibition of gingipain protease activities in coinfecting P. gingivalis abated the coaggregation and the enhancement of T. Forsythia phagocytosis. However, the direct effect of protease activities of gingipains on T. Forsythia seemed to be minimal. Although most of the phagocytosed T. Forsythia were cleared in infected macrophages, more T. Forsythia remained in cells coinfected with gingipain-expressing P. gingivalis than in cells coinfected with the gingipain-null mutant or infected only with T. Forsythia at 24 and 48 h post-infection. Collectively, these results suggest that P. gingivalis, mainly via its gingipains, alters the clearance of T. Forsythia, and provide some insights into the role of P. gingivalis as a keystone pathogen.
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Tannerella Forsythia GroEL induces inflammatory bone resorption and synergizes with interleukin-17.
Molecular oral microbiology, 2016Co-Authors: Youngjung Jung, Yujung Choi, Hae-ri Lee, Hye-kyoung Jun, Bongkyu ChoiAbstract:Tannerella Forsythia is a major periodontal pathogen, and T. Forsythia GroEL is a molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL-17) has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. Forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. Forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. Forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2 ) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. Forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. Forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. Tannerella Forsythia GroEL induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. Both T. Forsythia GroEL and IL-17 synergistically increased PGE2 production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. Forsythia GroEL injection, and simultaneous injection of T. Forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. Forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. Forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption.