The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Yiping W. Han - One of the best experts on this subject based on the ideXlab platform.
-
Fusobacterium nucleatum promotes colorectal cancer by inducing wnt β catenin modulator annexin a1
EMBO Reports, 2019Co-Authors: Mara R Rubinstein, Jung Eun Baik, Stephen M Lagana, Debashis Sahoo, Piero Dalerba, Timothy C Wang, Richard P Han, William Raab, Yiping W. HanAbstract:Abstract Fusobacterium nucleatum , a Gram‐negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre‐cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β‐catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up‐regulates Annexin A1 expression through E‐cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non‐cancerous cells. We therefore propose a “two‐hit” model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the “adenoma‐carcinoma” model and identifies microbes such as F. nucleatum as cancer “facilitators”.
-
Fusobacterium nucleatum a commensal turned pathogen
Current Opinion in Microbiology, 2015Co-Authors: Yiping W. HanAbstract:Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen associated with a wide spectrum of human diseases. This article reviews its implication in adverse pregnancy outcomes (chorioamnionitis, preterm birth, stillbirth, neonatal sepsis, preeclampsia), GI disorders (colorectal cancer, inflammatory bowel disease, appendicitis), cardiovascular disease, rheumatoid arthritis, respiratory tract infections, Lemierre's syndrome and Alzheimer's disease. The virulence mechanisms involved in the diseases are discussed, with emphasis on its colonization, systemic dissemination, and induction of host inflammatory and tumorigenic responses. The FadA adhesin/invasin conserved in F. nucleatum is a key virulence factor and a potential diagnostic marker for F. nucleatum-associated diseases.
-
signal peptide of fada adhesin from Fusobacterium nucleatum plays a novel structural role by modulating the filament s length and width
FEBS Letters, 2012Co-Authors: Stephanie Temoin, Menachem Shoham, Yiping W. HanAbstract:FadA, a novel adhesin of periodontal pathogen Fusobacterium nucleatum is composed of two forms, pre-FadA and mature FadA (mFadA), constituting the functional FadA complex (FadAc). By electron microscopy, we observed that mFadA formed uniformly long and thin filaments, while FadAc formed heterogeneous filaments of varying lengths and widths, as well as "knots". Mutants in signal peptide or in the non-alpha-helical loop retaining heterogeneous structures had binding activity while those forming aggregates or long filaments lost activity. These observations suggest short filaments and knots may be the active forms of FadA. This is the first demonstration that a signal peptide is required for the assembly of a bacterial adhesin.
Ervin I Weiss - One of the best experts on this subject based on the ideXlab platform.
-
mouse model of experimental periodontitis induced by porphyromonas gingivalis Fusobacterium nucleatum infection bone loss and host response
Journal of Clinical Periodontology, 2009Co-Authors: David Polak, Ervin I Weiss, Asaf Wilensky, Lior Shapira, Amal Halabi, Dita Goldstein, Yael HourihaddadAbstract:Aim: To compare the effect of oral infection with Porphyromonas gingivalis or Fusobacterium nucleatum versus infection with both bacteria on mouse periodontal tissues, and to characterize the inflammatory response. Materials and Methods: Mice were orally infected with P. gingivalis, F. nucleatum or both. At 42 days post-infection, alveolar bone loss was quantified using micro-computerized tomography. Tumour necrosis factor-α (TNF-α) and interleukin (IL)-1β levels induced by the infection were quantified using the subcutaneous chamber model. Results: Mice orally infected with F. nucleatum/P. gingivalis exhibited significantly more bone loss compared with that of mono-infected and sham-infected mice. F. nucleatum/P. gingivalis infection also increased the levels of TNF-α and IL1β compared with the levels found in the mono-infected groups. Conclusions: Polymicrobial infection with P. gingivalis/F. nucleatum aggravates alveolar bone loss and induces a stronger inflammatory response compared with that observed upon infection with either bacterium alone. The results suggest that oral infection of mice with a mixture of P. gingivalis and F. nucleatum may be superior to mono-infection models of experimental periodontitis.
-
mechanism of visible light phototoxicity on porphyromonas gingivalis and Fusobacterium nucleatum
Photochemistry and Photobiology, 2005Co-Authors: Osnat Feuerstein, Isaac Ginsburg, Eti Dayan, Dalya Veler, Ervin I WeissAbstract:Abstract Phototoxicity of visible light laser on the porphyrin-producing bacteria, Porphyromonas gingivalis, in the absence of photosensitizers and under aerobic conditions was shown in previous studies. Recently, we found that the noncoherent visible light sources at wavelengths of 400–500 nm, commonly used in restorative dentistry, induced a phototoxic effect on P. gingivalis, as well as on Fusobacterium nucleatum, and to a lesser extent on the Streptococci sp. To elucidate the mechanism of this phototoxic effect, P. gingivalis and F. nucleatum were exposed to light (1) under aerobic and anaerobic environments and (2) in the presence of scavengers of reactive oxygen species (ROS). Phototoxic effect was not observed when the bacteria were exposed to light under anaerobic conditions. Dimethyl thiourea, a hydroxyl radical scavenger, was effective in reducing phototoxicity (P ≤ 0.05). Other scavengers, such as catalase, superoxide dismutase and ascorbic acid, were less effective when applied separately. The...
-
phototoxic effect of visible light on porphyromonas gingivalis and Fusobacterium nucleatum an in vitro study
Photochemistry and Photobiology, 2004Co-Authors: Osnat Feuerstein, Nir Persman, Ervin I WeissAbstract:Abstract The antibacterial effect of visible light irradiation combined with photosensitizers has been reported. The objective of this was to test the effect of visible light irradiation without photosensitizers on the viability of oral microorganisms. Strains of Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans and Streptococcus faecalis in suspension or grown on agar were exposed to visible light at wavelengths of 400–500 nm. These wavelengths are used to photopolymerize composite resins widely used for dental restoration. Three photocuring light sources, quartz–tungsten–halogen lamp, light-emitting diode and plasma-arc, at power densities between 260 and 1300 mW/cm2 were used for up to 3 min. Bacterial samples were also exposed to a near-infrared diode laser (wavelength, 830 nm), using identical irradiation parameters for comparison. The results show that blue light sources exert a phototoxic effect on P. gingivalis and F. nucleatum. The minimal inhibitory dose for P. gingivalis a...
Ashu Sharma - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
Fusobacterium nucleatum and tannerella forsythia induce synergistic alveolar bone loss in a mouse periodontitis model
Infection and Immunity, 2012Co-Authors: Rajendra P Settem, Ahmed Taher Elhassan, Kiyonobu Honma, Graham P Stafford, Ashu SharmaAbstract:Tannerella forsythia is strongly associated with chronic periodontitis, an inflammatory disease of the tooth-supporting tissues, leading to tooth loss. Fusobacterium nucleatum, an opportunistic pathogen, is thought to promote dental plaque formation by serving as a bridge bacterium between early- and late-colonizing species of the oral cavity. Previous studies have shown that F. nucleatum species synergize with T. forsythia during biofilm formation and pathogenesis. In the present study, we showed that coinfection of F. nucleatum and T. forsythia is more potent than infection with either species alone in inducing NF-κB activity and proinflammatory cytokine secretion in monocytic cells and primary murine macrophages. Moreover, in a murine model of periodontitis, mixed infection with the two species induces synergistic alveolar bone loss, characterized by bone loss which is greater than the additive alveolar bone losses induced by each species alone. Further, in comparison to the single-species infection, mixed infection caused significantly increased inflammatory cell infiltration in the gingivae and osteoclastic activity in the jaw bones. These data show that F. nucleatum subspecies and T. forsythia synergistically stimulate the host immune response and induce alveolar bone loss in a murine experimental periodontitis model.
-
synergy between tannerella forsythia and Fusobacterium nucleatum in biofilm formation
Oral Microbiology and Immunology, 2005Co-Authors: Ashu Sharma, Satoru Inagaki, W Sigurdson, Howard K KuramitsuAbstract:During dental plaque formation, the interaction of different organisms is important in the development of complex communities. Fusobacterium nucleatum is considered a ‘bridge-organism’ that facilitates colonization of other bacteria by coaggregation-mediated mechanisms and possibly by making the environment conducive for oxygen intolerant anaerobes. These studies were carried out to determine whether coaggregation between F. nucleatum and Tannerella forsythia is important in the formation of mixed species biofilms. Further, the role of BspA protein, a surface adhesin of T. forsythia, in coaggregation and biofilm formation was investigated. The results showed the development of synergistic mixed biofilms of F. nucleatum and T. forsythia when these bacteria were cocultured. The BspA protein was not involved in biofilm formation. Though BspA plays a role in coaggregation with F. nucleatum, presumably other adhesins are also involved. The synergistic biofilm formation between the two species was dependent on cell–cell contact and soluble components of the bacteria were not required. This study demonstrates that there is a positive synergy between F. nucleatum and T. forsythia in the development of mixed biofilms and that the cell–cell interaction is essential for this phenomenon.
Mara R Rubinstein - One of the best experts on this subject based on the ideXlab platform.
-
Fusobacterium nucleatum promotes colorectal cancer by inducing wnt β catenin modulator annexin a1
EMBO Reports, 2019Co-Authors: Mara R Rubinstein, Jung Eun Baik, Stephen M Lagana, William J Raab, Debashis Sahoo, Piero Dalerba, Timothy C WangAbstract:Abstract Fusobacterium nucleatum , a Gram‐negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre‐cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β‐catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up‐regulates Annexin A1 expression through E‐cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non‐cancerous cells. We therefore propose a “two‐hit” model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the “adenoma‐carcinoma” model and identifies microbes such as F. nucleatum as cancer “facilitators”.
-
Fusobacterium nucleatum promotes colorectal cancer by inducing wnt β catenin modulator annexin a1
EMBO Reports, 2019Co-Authors: Mara R Rubinstein, Jung Eun Baik, Stephen M Lagana, Debashis Sahoo, Piero Dalerba, Timothy C Wang, Richard P Han, William Raab, Yiping W. HanAbstract:Abstract Fusobacterium nucleatum , a Gram‐negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre‐cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β‐catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up‐regulates Annexin A1 expression through E‐cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non‐cancerous cells. We therefore propose a “two‐hit” model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the “adenoma‐carcinoma” model and identifies microbes such as F. nucleatum as cancer “facilitators”.
-
Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating e cadherin β catenin signaling via its fada adhesin
Cell Host & Microbe, 2013Co-Authors: Mara R Rubinstein, Xiaowei WangAbstract:Summary Fusobacterium nucleatum ( Fn ) has been associated with colorectal cancer (CRC), but causality and underlying mechanisms remain to be established. We demonstrate that Fn adheres to, invades, and induces oncogenic and inflammatory responses to stimulate growth of CRC cells through its unique FadA adhesin. FadA binds to E-cadherin, activates β-catenin signaling, and differentially regulates the inflammatory and oncogenic responses. The FadA-binding site on E-cadherin is mapped to an 11-amino-acid region. A synthetic peptide derived from this region of E-cadherin abolishes FadA-induced CRC cell growth and oncogenic and inflammatory responses. The fadA gene levels in the colon tissue from patients with adenomas and adenocarcinomas are >10–100 times higher compared to normal individuals. The increased FadA expression in CRC correlates with increased expression of oncogenic and inflammatory genes. This study unveils a mechanism by which Fn can drive CRC and identifies FadA as a potential diagnostic and therapeutic target for CRC.
Timothy C Wang - One of the best experts on this subject based on the ideXlab platform.
-
Fusobacterium nucleatum promotes colorectal cancer by inducing wnt β catenin modulator annexin a1
EMBO Reports, 2019Co-Authors: Mara R Rubinstein, Jung Eun Baik, Stephen M Lagana, William J Raab, Debashis Sahoo, Piero Dalerba, Timothy C WangAbstract:Abstract Fusobacterium nucleatum , a Gram‐negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre‐cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β‐catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up‐regulates Annexin A1 expression through E‐cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non‐cancerous cells. We therefore propose a “two‐hit” model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the “adenoma‐carcinoma” model and identifies microbes such as F. nucleatum as cancer “facilitators”.
-
Fusobacterium nucleatum promotes colorectal cancer by inducing wnt β catenin modulator annexin a1
EMBO Reports, 2019Co-Authors: Mara R Rubinstein, Jung Eun Baik, Stephen M Lagana, Debashis Sahoo, Piero Dalerba, Timothy C Wang, Richard P Han, William Raab, Yiping W. HanAbstract:Abstract Fusobacterium nucleatum , a Gram‐negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre‐cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β‐catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up‐regulates Annexin A1 expression through E‐cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non‐cancerous cells. We therefore propose a “two‐hit” model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the “adenoma‐carcinoma” model and identifies microbes such as F. nucleatum as cancer “facilitators”.
