Effects of fluid shear stress on oral biofilm formation and composition and the transcriptional response of Streptococcus gordonii.

Biofilms are subjected to many environmental pressures that can influence community structure and physiology. In the oral cavity, and many other environments, biofilms are exposed to forces generated by fluid flow; however, our understanding of how oral biofilms respond to these forces remains limited. In this study, we developed a linear rocker model of fluid flow to study the impact of shear forces on Streptococcus gordonii and dental plaque-derived multispecies biofilms.

-acyl homoserine lactone signaling modulates bacterial community associated with human dental plaque.

-acyl homoserine lactones (AHLs) are small diffusible signaling molecules that mediate a cell density-dependent bacterial communication system known as quorum sensing (QS). AHL-mediated QS regulates gene expression to control many critical bacterial behaviors including biofilm formation, pathogenicity, and antimicrobial resistance. Dental plaque is a complex multispecies oral biofilm formed by successive colonization of the tooth surface by groups of commensal, symbiotic, and pathogenic bacteria, which can contribute to tooth decay and periodontal diseases.

Localization of the Remnant of a Cell Wall Sorting Signal and Its Interaction with a Sensor Kinase.

Sortases are highly conserved enzymes with endopeptidase and transpeptidase activities in Gram-positive bacteria. Sortase A cleaves within an LPXTG-motif and covalently crosslinks cell wall proteins to become anchored to the peptidoglycan of the cell wall. We showed that a peptide cleaved by sortase A from the C-terminus (C-pep) of the LPXTG-adhesin SspA intercalates in the cell membrane.

Depleting CD103+ resident memory T cells in vivo reveals immunostimulatory functions in oral mucosa.

The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the oral mucosa harbors CD8+ CD103+ resident memory T cells (TRM), which locally survey tissues without recirculating. Oral antigen re-encounter during the effector phase of immune responses potentiated TRM establishment within tongue, gums, palate, and cheek.

Intracellular calprotectin (S100A8/A9) facilitates DNA damage responses and promotes apoptosis in head and neck squamous cell carcinoma.

Objectives: In head and neck squamous cell carcinoma (HNSCC), poor prognosis and low survival rates are associated with downregulated calprotectin. Calprotectin (S100A8/A9) inhibits cancer cell migration and invasion and facilitates G2/M cell cycle arrest. We investigated whether S100A8/A9 regulates DNA damage responses (DDR) and apoptosis in HNSCC after chemoradiation.

Antimicrobial peptides: Defending the mucosal epithelial barrier.

The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes.

Streptococcus gordonii Poised for Glycan Feeding through a MUC5B-Discriminating, Lipoteichoic Acid-Mediated Outside-In Signaling Circuit.

Many oral bacteria employ cell wall-anchored adhesins to bind to the salivary films coating the teeth and mucosal surfaces. Surface binding prevents clearance and facilitates catabolism of salivary film glycoproteins. We asked whether Streptococcus gordonii adhesin expression changes in response to surface salivary cues using a eukaryote-like, outside-in recognition and signaling circuit.

In vitro physicochemical characterization of five root canal sealers and their influence on an ex vivo oral multi-species biofilm community.

Aim: To evaluate the physicochemical properties of five root canal sealers and assess their effect on an ex vivo dental plaque-derived polymicrobial community.

Methodology: Dental plaque-derived microbial communities were exposed to the sealers (AH Plus [AHP], GuttaFlow Bioseal [GFB], Endoseal MTA [ESM], Bio-C sealer [BCS] and BioRoot RCS [BRR]) for 3, 6 and 18 h. The sealers' effect on the biofilm biomass and metabolic activity was quantified using crystal violet (CV) staining and MTT assay, respectively.

Calprotectin (S100A8/A9) Is an Innate Immune Effector in Experimental Periodontitis.

Upregulated in inflammation, calprotectin (complexed S100A8 and S100A9; S100A8/A9) functions as an innate immune effector molecule, promoting inflammation, and also as an antimicrobial protein. We hypothesized that antimicrobial S100A8/A9 would mitigate change to the local microbial community and promote resistance to experimental periodontitis . To test this hypothesis, S100A9 and wild-type (WT; S100A9) C57BL/6 mice were compared using a model of ligature-induced periodontitis.

Uncovering Roles of Streptococcus gordonii SrtA-Processed Proteins in the Biofilm Lifestyle.

is a commensal oral organism. Harmless in the oral cavity, is an opportunistic pathogen. adheres to body surfaces using surface adhesive proteins (adhesins), which are critical to subsequent formation of biofilm communities.

Streptococcus gordonii Type I Lipoteichoic Acid Contributes to Surface Protein Biogenesis.

Lipoteichoic acid (LTA) is an abundant polymer of the Gram-positive bacterial cell envelope and is essential for many species. Whereas the exact function of LTA has not been elucidated, loss of LTA in some species affects hydrophobicity, biofilm formation, and cell division. Using a viable LTA-deficient strain of the human oral commensal , we demonstrated that LTA plays an important role in surface protein presentation.

An intramembrane sensory circuit monitors sortase A-mediated processing of streptococcal adhesins.

Bacterial adhesins mediate adhesion to substrates and biofilm formation. Adhesins of the LPXTG family are posttranslationally processed by the cell membrane-localized peptidase sortase A, which cleaves the LPXTG motif. This generates a short C-terminal peptide (C-pep) that remains in the cell membrane, whereas the mature adhesin is incorporated into the cell wall.

The innate host response in caries and periodontitis.

Introduction: Innate immunity rapidly defends the host against infectious insults. These reactions are of limited specificity and exhaust without providing long-term protection. Functional fluids and effector molecules contribute to the defence against infectious agents, drive the immune response, and direct the cellular players.

Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the Joint EFP/ORCA workshop on the boundaries between caries and periodontal disease.

Background And Aims: The scope of this working group was to review (1) ecological interactions at the dental biofilm in health and disease, (2) the role of microbial communities in the pathogenesis of periodontitis and caries, and (3) the innate host response in caries and periodontal diseases.

Results And Conclusions: A health-associated biofilm includes genera such as Neisseria, Streptococcus, Actinomyces, Veillonella and Granulicatella. Microorganisms associated with both caries and periodontal diseases are metabolically highly specialized and organized as multispecies microbial biofilms.

Oncolytic adenoviruses targeted to Human Papilloma Virus-positive head and neck squamous cell carcinomas.

Objectives: In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins.

Methods: Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells.

Autonomous immunity in mucosal epithelial cells: fortifying the barrier against infection.

Mucosal epithelial cells express an autonomous innate immune response that controls the overgrowth of invaded bacteria, mitigates the harmful effects of the bacteria carried within, and does not rely on other external arms of the immune response. Epithelial cell autonomous innate immunity "respects" the social biology of invading bacteria to achieve symbiosis, and is the primary protective mechanism against pathogens.

Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC.

Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells.

The oral microbiome and the immunobiology of periodontal disease and caries.

The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth.

S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells.

Intracellular calprotectin (S100A8/A9) functions in the control of the cell cycle checkpoint at G2/M. Dysregulation of S100A8/A9 appears to cause loss of the checkpoint, which frequently characterizes head and neck squamous cell carcinoma (HNSCC). In the present study, we analyzed carcinoma cells for other S100A8/A9-directed changes in malignant phenotype.

Augmentation of epithelial resistance to invading bacteria by using mRNA transfections.

To protect against invading bacteria, oral epithelial cells appear to use two effector antimicrobial peptides (AMPs): calprotectin (S100A8-S100A9 heterodimer [S100A8/A9]) in the cytosol and cathelicidin antimicrobial protein (CAMP) in endosomes. We sought to learn whether innate immunity might be augmented benignly to increase resistance against invasive bacteria. Epithelial cells were transiently transfected with mRNA constructs containing either the CAMP, S100A8, and S100A9 open reading frames, A8-IRES-A9 (fusion sequence), or A8-nIRES-A9 (fusion with native internal ribosome entry site [IRES] sequence).

S100A8/A9 (calprotectin) negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma.

Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC) and other cancers. S100A8/A9 (calprotectin) is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels.

Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases.

Background: There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions.

Aim: To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4.

Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases.

Background: There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions.

Aim: To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4.