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

(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.

Download Full-text

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

Journal of Bacteriology ◽

10.1128/jb.01631-09 ◽

2010 ◽

Vol 192 (12) ◽

pp. 2965-2972 ◽

Cited By ~ 89

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.

Download Full-text

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

Journal of Dental Research ◽

10.1177/0022034509334846 ◽

2009 ◽

Vol 88 (4) ◽

pp. 333-338 ◽

Cited By ~ 37

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.

Download Full-text

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

Infection and Immunity ◽

10.1128/iai.66.10.4729-4732.1998 ◽

1998 ◽

Vol 66 (10) ◽

pp. 4729-4732 ◽

Cited By ~ 193

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.

Download Full-text

Metabolic and Community Synergy of Oral Bacteria in Colorectal Cancer

mSphere ◽

10.1128/msphere.00102-16 ◽

2016 ◽

Vol 1 (3) ◽

Cited By ~ 62

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.

Download Full-text

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

The Open Dentistry Journal ◽

10.2174/1874210602115010367 ◽

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.

Download Full-text

Role of Oral Microbiota in Cancer Development

Microorganisms ◽

10.3390/microorganisms7010020 ◽

2019 ◽

Vol 7 (1) ◽

pp. 20 ◽

Cited By ~ 57

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.

Download Full-text

IL-36γ is a pivotal inflammatory player in periodontitis-associated bone loss

Scientific Reports ◽

10.1038/s41598-019-55595-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Alexandra Cloitre ◽

Boris Halgand ◽

Sophie Sourice ◽

Jocelyne Caillon ◽

Olivier Huck ◽

...

Keyword(s):

Bone Resorption ◽

Alveolar Bone ◽

Chronic Inflammatory Disease ◽

Oral Bacteria ◽

Oral Epithelial Cells ◽

Tnf Α ◽

Tlr2 Activation ◽

Oral Epithelial

AbstractPeriodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1β, IL-6, TNF-α and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36α/IL-36β/IL-36γ/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. We showed here that IL-36γ mRNA gingival expression is higher in periodontitis patients, whereas IL-36β and IL-36Ra mRNA expression are lower compared to healthy controls. Interestingly, the elevated IL-36γ expression in patients is positively correlated with the RANKL/OPG ratio, an index of bone resorption. In vitro, IL-36γ expression was induced through TLR2 activation in primary OECs infected with P. gingivalis but not in gingival fibroblasts, the most widespread cell type in gingival connective tissue. In OECs, recombinant IL-36γ enhanced the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-36γ), of TLR2 and importantly, the RANKL/OPG ratio. These findings suggest that IL-36γ could be a pivotal inflammatory player in periodontitis by perpetuating gingival inflammation and its associated alveolar bone resorption and could be a relevant therapeutic target.

Download Full-text

Protein interactions between the oral bacteria Fusobacterium nucleatum and Porphyromonas gingivalis in biofilm and planktonic culture

10.1101/2020.11.23.393850 ◽

2020 ◽

Author(s):

Marwan Mansoor Ali Mohammed ◽

Veronika Kuchařová Pettersen ◽

Audun H. Nerland ◽

Harald G. Wiker ◽

Vidar Bakken

Keyword(s):

Porphyromonas Gingivalis ◽

Protein Interactions ◽

Fusobacterium Nucleatum ◽

Oral Bacteria ◽

Cell Contact ◽

P Value ◽

Bacterial Cells ◽

Label Free ◽

Planktonic Culture ◽

Oral Biofilm

AbstractThe opportunistic pathogens Fusobacterium nucleatum and Porphyromonas gingivalis are Gram-negative bacteria associated with oral biofilm and periodontal disease. Although liquid cultures are often the preferred cultivation method in microbiology, bacterial cells in biofilm adopt a profoundly different phenotype reflecting the close cell-to-cell contact compare to their planktonic counterparts. To investigate F. nucleatum and P. gingivalis interactions relevant in biofilm formation, we applied liquid chromatography-tandem mass spectrometry to determine the expressed proteome of F. nucleatum and P. gingivalis cells that were grown either as biofilm or in planktonic culture, and individually or together.The proteomic analyses detected 1,322 F. nucleatum and 966 P. gingivalis proteins. We statistically compared the proteins label-free quantitative (LFQ) intensities between biofilm and planktonic culture and identified significant changes (p-value ≤0.05) in 0,4% F. nucleatum proteins, 7% P. gingivalis proteins, and more than 14% of all proteins in the dual-species model. For both species, proteins involved in vitamin B2 (riboflavin) metabolic process had significantly increased levels in the biofilm condition. In both mono- and dual-species biofilm models, P. gingivalis increased the production of proteins functional in translation, oxidation-reduction, and amino acid metabolism, when compared to planktonic cultures. However, when we compared LFQ intensities between mono- and dual-species models, over 90% of the significantly changed P. gingivalis proteins had their levels reduced in biofilm and planktonic settings of the dual-species model.Our findings suggest that the two bacteria interact with each other at the protein level and indicate that P. gingivalis reduces the production of multiple proteins because of more favourable growth conditions provided by F. nucleatum presence. The results highlight the complex interactions of bacteria contributing to oral biofilm, which need to be considered in the design of future prevention strategies.

Download Full-text

A Role of Oral Bacteria in Bisphosphonate-induced Osteonecrosis of the Jaw

Journal of Dental Research ◽

10.1177/0022034511420430 ◽

2011 ◽

Vol 90 (11) ◽

pp. 1339-1345 ◽

Cited By ~ 52

Author(s):

H. Mawardi ◽

G. Giro ◽

M. Kajiya ◽

K. Ohta ◽

S. Almazrooa ◽

...

Keyword(s):

Tooth Extraction ◽

Healing Process ◽

Fusobacterium Nucleatum ◽

Osteonecrosis Of The Jaw ◽

Oral Bacteria ◽

Wound Healing Process ◽

Cell Growth And Migration ◽

Periodontal Tissues

No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.

Download Full-text

Oral Surgery Procedures in a Patient with Hajdu-Cheney Syndrome Treated with Denosumab—A Rare Case Report

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18179099 ◽

2021 ◽

Vol 18 (17) ◽

pp. 9099

Author(s):

Magdalena Kaczoruk-Wieremczuk ◽

Paulina Adamska ◽

Łukasz Jan Adamski ◽

Piotr Wychowański ◽

Barbara Alicja Jereczek-Fossa ◽

...

Keyword(s):

Case Report ◽

Rare Case ◽

Alveolar Bone ◽

Oral Surgery ◽

Nuclear Factor Κb ◽

Osteonecrosis Of The Jaw ◽

Prosthetic Reconstruction ◽

Dental Procedures ◽

Rare Case Report ◽

Medical University

Background: Hajdu-Cheney syndrome (HCS) is a very rare autosomal-dominant congenital disease associated with mutations in the NOTCH2 gene. This disorder affects the connective tissue and is characterized by severe bone resorption. Hajdu-Cheney syndrome most frequently affects the head and feet bones (acroosteolysis). Case report: We present an extremely rare case of a 34-year-old male with Hajdu-Cheney syndrome. The patient was admitted to the Department of Oral Surgery, Medical University of Gdańsk, in order to perform the extraction of three teeth. These teeth were not eligible for conservative treatment and prosthetic reconstruction. The patient was treated with denosumab (angiogenesis and receptor activator of nuclear factor-κB RANK ligand inhibitor, RANKL). Discussion: Denosumab is a monoclonal antibody against RANKL. This drug works through a suppression of osteoclast activity. In cases of patients in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated, denosumab has been approved for the treatment off-label. In patients receiving denosumab, a delayed wound healing in the oral cavity and osteonecrosis may occur. Dental procedures involving the alveolar bone process (tooth extractions and bone alveoloplasty) may be a risk factor for medication-related osteonecrosis of the jaw (MRONJ). Spontaneous osteonecrosis is rarely observed. MRONJ consists of the destruction of exposed bone, with the exposure persisting for a minimum of 6–8 weeks. This is the first article about an HCS patient treated with denosumab who underwent invasive oral surgery procedures. This case report highlights the difficulties for professionals occurring during the oral surgery procedures in such patients.

Download Full-text