scholarly journals TGF-β1 Inhibits TLR-mediated Odontoblast Responses to Oral Bacteria

2009 ◽  
Vol 88 (4) ◽  
pp. 333-338 ◽  
Author(s):  
O.V. Horst ◽  
K.A. Tompkins ◽  
S.R. Coats ◽  
P.H. Braham ◽  
R.P. Darveau ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tissue Repair ◽  
Lactobacillus Casei ◽  
Tooth Development ◽  
Fusobacterium Nucleatum ◽  
Poor Response ◽  
Oral Bacteria ◽  
Cellular Processes ◽  
Tgf Β1

TGF-β1 exerts diverse functions in tooth development and tissue repair, but its role in microbial defenses of the tooth is not well-understood. Odontoblasts extending their cellular processes into the dentin are the first cells to recognize signals from TGF-β1 and bacteria in carious dentin. This study aimed to determine the role of TGF-β1 in modulating odontoblast responses to oral bacteria. We show that these responses depend upon the expression levels of microbial recognition receptors TLR2 and TLR4 on the cell surface. Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum activated both TLRs, but TLR4 played a greater role. Lack of cell-surface TLR2 was associated with poor response to Streptococcus mutans, Enterococcus faecalis, and Lactobacillus casei. TGF-β1 inhibited TLR2 and TLR4 expression and attenuated odontoblast responses. Our findings suggest that the balance between TLR-mediated inflammation and TGF-β1 anti-inflammatory activity plays an important role in pulpal inflammation.

scholarly journals FOXO3a is stabilized by USP18-mediated de-ISGylation and inhibits TGF-β1-induced fibronectin expression

2019 ◽  
Vol 68 (3) ◽  
pp. 786-791 ◽  
Author(s):  
Ban Wang ◽  
Yanhui Li ◽  
Heather Wang ◽  
Jing Zhao ◽  
Yutong Zhao ◽  
...  
Keyword(s):  
Half Life ◽  
Transforming Growth Factor ◽  
Fibroblast Cells ◽  
Post Translational Modification ◽  
Human Lung Fibroblast ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Fibronectin Expression ◽  
Tgf Β1

FOXO3a belongs to a family of transcription factors characterized by a conserved forkhead box DNA-binding domain. It has been known to regulate various cellular processes including cell proliferation, apoptosis and differentiation. Post-translational modifications of FOXO3a and their roles in the regulation of FOXO3a activity have been well-documented. FOXO3a can be phosphorylated, acetylated and ubiquitinated, however, the ISGylation of FOXO3a has not been reported. Protein overexpression, ISGylation and half-life were measured to determine the post-translational modification of FOXO3a. Human fibroblast cells were treated with transforming growth factor (TGF)-β1 to determine the role of FOXO3a ISGylation in TGF-β1 signaling. FOXO3a’s half-life is around 3.7 hours. Inhibition of the proteasome, not lysosome, extends its half-life. ISGylation, but not ubiquitination of FOXO3a, is increased in the presence of the proteasome inhibitor. Overexpression of ISG15 increases FOXO3a degradation, while overexpression of USP18 stabilizes FOXO3a through de-ISGylation. These results suggest that FOXO3a is degraded in the ISGylation and proteasome system, which can be reversed by USP18, an ISG15-specific deubiquitinase. This study reveals a new molecular mechanism by which ISGylation regulates FOXO3a degradation. Furthermore, we show that the overexpression of FOXO3a attenuated TGF-β1-induced fibronectin expression in human lung fibroblast cells without altering Smad2/3 expression and activation. FOXO3a can be ISGylated, which can regulate FOXO3a stability. USP18/FOXO3a pathway is a potential target for treating TGF-β1-mediated fibrotic diseases such as idiopathic pulmonary fibrosis.

scholarly journals Transcriptomic Studies Reveal that the Rhizobium leguminosarum Serine/Threonine Protein Phosphatase PssZ has a Role in the Synthesis of Cell-Surface Components, Nutrient Utilization, and Other Cellular Processes

2019 ◽  
Vol 20 (12) ◽  
pp. 2905 ◽  
Author(s):  
Paulina Lipa ◽  
José-María Vinardell ◽  
Monika Janczarek
Keyword(s):  
Cell Surface ◽  
Rhizobium Leguminosarum ◽  
Cell Signalling ◽  
Nutrient Utilization ◽  
Transport Systems ◽  
Symbiotic Associations ◽  
Cellular Processes ◽  
Successful Infection ◽  
Surface Polysaccharides

Rhizobium leguminosarum bv. trifolii is a soil bacterium capable of establishing symbiotic associations with clover plants (Trifolium spp.). Surface polysaccharides, transport systems, and extracellular components synthesized by this bacterium are required for both the adaptation to changing environmental conditions and successful infection of host plant roots. The pssZ gene located in the Pss-I region, which is involved in the synthesis of extracellular polysaccharide, encodes a protein belonging to the group of serine/threonine protein phosphatases. In this study, a comparative transcriptomic analysis of R. leguminosarum bv. trifolii wild-type strain Rt24.2 and its derivative Rt297 carrying a pssZ mutation was performed. RNA-Seq data identified a large number of genes differentially expressed in these two backgrounds. Transcriptome profiling of the pssZ mutant revealed a role of the PssZ protein in several cellular processes, including cell signalling, transcription regulation, synthesis of cell-surface polysaccharides and components, and bacterial metabolism. In addition, we show that inactivation of pssZ affects the rhizobial ability to grow in the presence of different sugars and at various temperatures, as well as the production of different surface polysaccharides. In conclusion, our results identified a set of genes whose expression was affected by PssZ and confirmed the important role of this protein in the rhizobial regulatory network.

scholarly journals Central Role of the Early Colonizer Veillonella sp. in Establishing Multispecies Biofilm Communities with Initial, Middle, and Late Colonizers of Enamel

2010 ◽  
Vol 192 (12) ◽  
pp. 2965-2972 ◽  
Author(s):  
Saravanan Periasamy ◽  
Paul E. Kolenbrander
Keyword(s):  
Lactic Acid ◽  
Fluorescent Antibody ◽  
Fusobacterium Nucleatum ◽  
Single Species ◽  
Oral Bacteria ◽  
Flow Cells ◽  
Significant Growth ◽  
Dental Biofilm ◽  
Antibody Staining

ABSTRACT Human dental biofilm communities comprise several species, which can interact cooperatively or competitively. Bacterial interactions influence biofilm formation, metabolic changes, and physiological function of the community. Lactic acid, a common metabolite of oral bacteria, was measured in the flow cell effluent of one-, two- and three-species communities growing on saliva as the sole nutritional source. We investigated single-species and multispecies colonization by using known initial, early, middle, and late colonizers of enamel. Fluorescent-antibody staining and image analysis were used to quantify the biomass in saliva-fed flow cells. Of six species tested, only the initial colonizer Actinomyces oris exhibited significant growth. The initial colonizer Streptococcus oralis produced lactic acid but showed no significant growth. The early colonizer Veillonella sp. utilized lactic acid in two- and three-species biofilm communities. The biovolumes of all two-species biofilms increased when Veillonella sp. was present as one of the partners, indicating that this early colonizer promotes mutualistic community development. All three-species combinations exhibited enhanced growth except one, i.e., A. oris, Veillonella sp., and the middle colonizer Porphyromonas gingivalis, indicating specificity among three-species communities. Further specificity was seen when Fusobacterium nucleatum (a middle colonizer), Aggregatibacter actinomycetemcomitans (a late colonizer), and P. gingivalis did not grow with S. oralis in two-species biofilms, but inclusion of Veillonella sp. resulted in growth of all three-species combinations. We propose that commensal veillonellae use lactic acid for growth in saliva and that they communicate metabolically with initial, early, middle, and late colonizers to establish multispecies communities on enamel.

scholarly journals Role of Fusobacterium nucleatum and Coaggregation in Anaerobe Survival in Planktonic and Biofilm Oral Microbial Communities during Aeration

1998 ◽  
Vol 66 (10) ◽  
pp. 4729-4732 ◽  
Author(s):  
David J. Bradshaw ◽  
Philip D. Marsh ◽  
G. Keith Watson ◽  
Clive Allison
Keyword(s):  
Anaerobic Bacteria ◽  
Fusobacterium Nucleatum ◽  
Oral Bacteria ◽  
Obligate Anaerobe ◽  
Obligately Anaerobic ◽  
Prevotella Nigrescens ◽  
Tolerant Species ◽  
Species Pairs ◽  
Planktonic Phase

ABSTRACT Coaggregation is a well-characterized phenomenon by which specific pairs of oral bacteria interact physically. The aim of this study was to examine the patterns of coaggregation between obligately anaerobic and oxygen-tolerant species that coexist in a model oral microbial community. Obligate anaerobes other than Fusobacterium nucleatum coaggregated only poorly with oxygen-tolerant species. In contrast, F. nucleatum was able to coaggregate not only with both oxygen-tolerant and other obligately anaerobic species but also with otherwise-noncoaggregating obligate anaerobe–oxygen-tolerant species pairs. The effects of the presence or absence of F. nucleatum on anaerobe survival in both the biofilm and planktonic phases of a complex community of oral bacteria grown in an aerated (gas phase, 200 ml of 5% CO2 in air · min−1) chemostat system were then investigated. In the presence of F. nucleatum, anaerobes persisted in high numbers (>107 · ml−1 in the planktonic phase and >107 · cm−2 in 4-day biofilms). In an equivalent culture in the absence of F. nucleatum, the numbers of black-pigmented anaerobes (Porphyromonas gingivalis and Prevotella nigrescens) were significantly reduced (P ≤ 0.001) in both the planktonic phase and in 4-day biofilms, while the numbers of facultatively anaerobic bacteria increased in these communities. Coaggregation-mediated interactions between F. nucleatum and other species facilitated the survival of obligate anaerobes in aerated environments.

scholarly journals Metabolic and Community Synergy of Oral Bacteria in Colorectal Cancer

mSphere ◽  
2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Kaitlin J. Flynn ◽  
Nielson T. Baxter ◽  
Patrick D. Schloss
Keyword(s):  
Colorectal Cancer ◽  
Fusobacterium Nucleatum ◽  
Oral Bacteria ◽  
Oral Microbiota ◽  
Community Members ◽  
Content Type ◽  
Bacterial Physiology ◽  
Oral Biofilms ◽  
Two Factors

ABSTRACT The oral periodontopathic bacterium Fusobacterium nucleatum has been repeatedly associated with colorectal tumors. Molecular analysis has identified specific virulence factors that promote tumorigenesis in the colon. However, other oral community members, such as members of the Porphyromonas spp., are also found with F. nucleatum on colonic tumors, and thus, narrow studies of individual pathogens do not take community-wide virulence properties into account. A broader view of oral bacterial physiology and pathogenesis identifies two factors that could promote colonization and persistence of oral bacterial communities in the colon. The polymicrobial nature of oral biofilms and the asaccharolytic metabolism of many of these species make them well suited to life in the microenvironment of colonic lesions. Consideration of these two factors offers a novel perspective on the role of oral microbiota in the initiation, development, and treatment of colorectal cancer.

scholarly journals The Role of Periodontopathogens and Oral Microbiome in the Progression of Oral Cancer. A Review

2021 ◽  
Vol 15 (1) ◽  
pp. 367-376
Author(s):  
Julián F. Beltran ◽  
SM Viafara-Garcia ◽  
Alberto P. Labrador ◽  
Johan Basterrechea
Keyword(s):  
Periodontal Disease ◽  
Cell Cancer ◽  
Bacterial Chemotaxis ◽  
Fusobacterium Nucleatum ◽  
Oral Bacteria ◽  
Oral Microbiome ◽  
Chronic Periodontal Disease ◽  
Oral Squamous Cell Cancer ◽  
The Relationship

Chronic periodontal disease and oral bacteria dysbiosis can lead to the accumulation of genetic mutations that eventually stimulate Oral Squamous Cell Cancer (OSCC). The annual incidence of OSCC is increasing significantly, and almost half of the cases are diagnosed in an advanced stage. Worldwide there are more than 380,000 new cases diagnosed every year, and a topic of extensive research in the last few years is the alteration of oral bacteria, their compositional changes and microbiome. This review aims to establish the relationship between bacterial dysbiosis and OSCC. Several bacteria implicated in periodontal disease, including Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, and some Streptococcus species, promote angiogenesis, cell proliferation, and alteration in the host defense process; these same bacteria have been present in different stages of OSCC. Our review showed that genes involved in bacterial chemotaxis, the lipopolysaccharide (LPS) of the cell wall membrane of gram negatives bacteria, were significantly increased in patients with OSCC. Additionally, some bacterial diversity, particularly with Firmicutes, and Actinobacteria species, has been identified in pre-cancerous stage samples. This review suggests the importance of an early diagnosis and more comprehensive periodontal therapy for patients by the dental care professional.

scholarly journals Role of Oral Microbiota in Cancer Development

2019 ◽  
Vol 7 (1) ◽  
pp. 20 ◽  
Author(s):  
Tomasz Karpiński
Keyword(s):  
Cell Proliferation ◽  
Porphyromonas Gingivalis ◽  
Fusobacterium Nucleatum ◽  
Oral Bacteria ◽  
Cancer Development ◽  
Oral Microbiota ◽  
Cellular Apoptosis ◽  
Bacterial Stimulation ◽  
Specific Species

Nowadays cancer is the second main cause of death in the world. The most known bacterial carcinogen is Helicobacter pylori. Pathogens that can have an impact on cancer development in the gastrointestinal tract are also found in the oral cavity. Some specific species have been identified that correlate strongly with oral cancer, such as Streptococcus sp., Peptostreptococcus sp., Prevotella sp., Fusobacterium sp., Porphyromonas gingivalis, and Capnocytophaga gingivalis. Many works have also shown that the oral periopathogens Fusobacterium nucleatum and Porphyromonas gingivalis play an important role in the development of colorectal and pancreatic cancer. Three mechanisms of action have been suggested in regard to the role of oral microbiota in the pathogenesis of cancer. The first is bacterial stimulation of chronic inflammation. Inflammatory mediators produced in this process cause or facilitate cell proliferation, mutagenesis, oncogene activation, and angiogenesis. The second mechanism attributed to bacteria that may influence the pathogenesis of cancers by affecting cell proliferation is the activation of NF-κB and inhibition of cellular apoptosis. In the third mechanism, bacteria produce some substances that act in a carcinogenic manner. This review presents potentially oncogenic oral bacteria and possible mechanisms of their action on the carcinogenesis of human cells.

scholarly journals Fusobacterium nucleatum Promotes the Progression of Colorectal Cancer Through Cdk5-Activated Wnt/β-Catenin Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiang Li ◽  
Jiepeng Huang ◽  
Tingting Yu ◽  
Xiaoting Fang ◽  
Liqin Lou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Fusobacterium Nucleatum ◽  
Underlying Mechanism ◽  
Valuable Insight ◽  
Direct Role ◽  
Cellular Processes ◽  
And Migration

Background/AimsGrowing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/β-catenin signaling pathway.Materials and MethodsCRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations.ResultsThe abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/β-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/β-catenin signaling in relation to the progression of CRC.ConclusionThe results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/β-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.

scholarly journals Matrix-Bound Zolzoledronate Enhances the Biofilm Colonization of Hydroxyapatite: Effects on Osteonecrosis

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1380
Author(s):  
Ranya Elsayed ◽  
Ahmed El-Awady ◽  
Christopher Cutler ◽  
Zoya Kurago ◽  
Mahmoud Elashiry ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Fusobacterium Nucleatum ◽  
Osteonecrosis Of The Jaw ◽  
Oral Bacteria ◽  
Defect Model ◽  
Oral Biofilm ◽  
Bacterial Proliferation ◽  
Dental Procedures ◽  
Matrix Bound

(1) Background: The aim of this study was to test whether matrix-bound zoledronate (zol) molecules enhanced the oral biofilm colonization of a mineralized matrix, rendering the alveolar bone more susceptible to medication-related osteonecrosis of the jaw (MRONJ) following invasive dental procedures. (2) Methods: We tested the effect of matrix-bound zol on the growth and attachment of Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn) and Actinomyces israelii (Ai), and whether the nitrogen-containing component of zol contributed to such effect. The role of oral bacteria in the induction of osteonecrosis was then tested using an extra-oral bone defect model. (3) Results: The attachment of biofilm to hydroxyapatite discs increased when the discs were pre-treated with zol. Bacterial proliferation was not affected. Matrix-bound zol was more potent than non-nitrogen-containing etidronate in enhancing the colonization. Stimulation was dampened by pre-treating the bacteria with histidine. The delivery of oral biofilm to a tibial defect caused osteonecrosis in zol-treated rats. (4) Conclusions: We conclude that matrix-bound zol enhances the oral biofilm colonization of hydroxyapatite. This enhancement depended on the presence of the nitrogen-containing group. The oral biofilm rendered the extra-oral bone susceptible to medication-related osteonecrosis, suggesting that it has an important role in the induction of MRONJ.

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