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Clinical Oral Investigations Oct 2023This study is aimed at determining the effect of concomitant antimicrobial photodynamic therapy (aPTD) on periodontal disease and glycaemic control in patients with type... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study is aimed at determining the effect of concomitant antimicrobial photodynamic therapy (aPTD) on periodontal disease and glycaemic control in patients with type 2 diabetes mellitus (T2DM).
MATERIALS AND METHODS
Twenty-four patients with T2DM were enrolled in the study. Periodontal clinical parameters were assessed by measuring probing pocket depth (PPD), clinical attachment loss (CAL), gingival recession (GR), full-mouth bleeding score (FMBS), full-mouth plaque score (FMPS), and full-mouth sulcus bleeding score (FMSBS). Glycated haemoglobin A1c (HbA1c) was measured. To determine the presence of the following periodontal pathogenic bacteria, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, subgingival plaque samples were taken from two periodontal pockets per jaw with the greatest PPD using paper tips. Patients were randomly divided into the test and control group. In the test group, full-mouth disinfection was performed in combination with aPTD. In the control group, only full-mouth disinfection was performed.
RESULTS
The results showed an improvement in periodontal clinical parameters in both groups. The difference between the groups in favour of the test group was statistically significant for BOP. The HbA1c level decreased in both groups. The difference was not statistically significant. The results of the microbiological analysis suggest that the presence of periodontal pathogenic bacteria is lower with additional antimicrobial photodynamic therapy with statistically significant difference for T. forsythia.
CONCLUSIONS
Additional aPDT causes a significant reduction in BoP in the proportion of positive sites for periodontal pathogens.
TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT05816941.
CLINICAL RELEVANCE
aPTD is a noninvasive adjunctive therapy that can positively influence the periodontal treatment outcome.
Topics: Humans; Glycemic Control; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Periodontal Diseases; Photochemotherapy; Porphyromonas gingivalis; Anti-Infective Agents; Aggregatibacter actinomycetemcomitans; Dental Scaling; Chronic Periodontitis
PubMed: 37672083
DOI: 10.1007/s00784-023-05239-0 -
Molecular Oral Microbiology Jun 2020Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism... (Review)
Review
Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism produces a number of virulence factors, all of which provide some advantage to the bacterium. Several studies have demonstrated that clinical isolates from diseased patients, particularly those of African descent, frequently belong to specific clones of A. actinomycetemcomitans that produce significantly higher amounts of a protein exotoxin belonging to the repeats-in-toxin (RTX) family, leukotoxin (LtxA), whereas isolates from healthy patients harbor minimally leukotoxic strains. This finding suggests that LtxA might play a key role in A. actinomycetemcomitans pathogenicity. Because of this correlation, much work over the past 30 years has been focused on understanding the mechanisms by which LtxA interacts with and kills host cells. In this article, we review those findings, highlight the remaining open questions, and demonstrate how knowledge of these mechanisms, particularly the toxin's interactions with lymphocyte function-associated antigen-1 (LFA-1) and cholesterol, enables the design of targeted anti-LtxA strategies to prevent/treat disease.
Topics: Aggregatibacter actinomycetemcomitans; Exotoxins; Humans; Lymphocyte Function-Associated Antigen-1; Virulence Factors
PubMed: 32061022
DOI: 10.1111/omi.12284 -
F1000Research 2022A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora... (Observational Study)
Observational Study
A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora and expression of angiotensin-converting enzyme 2 ( ) remains to be established. In this observational study, we collected saliva from patients with COVID-19 and evaluated the relationship between expression and as well as with selected gram-negative bacteria ( , , and ). We investigated how this may be directly or indirectly involved in oral dysbiosis in patients with COVID-19. We included 23 hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, with six healthy participants serving as controls. Saliva and tongue surface swabs were collected from patients with diabetes (DG) and without diabetes (NDG) and subject controls. Using quantitative PCR (qPCR) we assessed the mRNA expression of , the abundance of , and the transcription levels of its biofilm-associated genes, agglutinin-like protein 3 ( ), hyphal wall protein 1 ( ), and yeast-form wall protein 1 ( ). We also counted the relative proportion of the three selected gram-negative oral bacteria in saliva. All analyses were performed to determine the relationship between expression and and gram-negative bacteria. mRNA expression was significantly higher in tongue swab samples than in saliva. However, no significant difference was observed between the patient groups. Conversely, DG patients had a significantly higher abundance of in saliva compared to NDG patients and control group patients. The correlation and sensitivity/specificity relationship between expression and or the selected oral bacteria were also observed. The data show that expression can be detected in saliva of patients with COVID-19 and its association with and gram-negative oral bacteria might contribute toward developing an oral dysbiosis based predictor for prognosis of COVID-19 severity.
Topics: Actins; Agglutinins; Aggregatibacter actinomycetemcomitans; Angiotensin-Converting Enzyme 2; COVID-19; Candida albicans; Dysbiosis; Humans; RNA, Messenger; SARS-CoV-2; Saliva
PubMed: 36112976
DOI: 10.12688/f1000research.111965.2 -
PloS One 2019Adjunctive use of antibiotics in periodontal treatment have limitations and disadvantages including bacterial resistance. Antimicrobial peptides (AMPs) are potential new...
Adjunctive use of antibiotics in periodontal treatment have limitations and disadvantages including bacterial resistance. Antimicrobial peptides (AMPs) are potential new agents that can combat bacterial infection. In this study, antimicrobial activity of different concentrations of conventional antibiotics minocycline (MH), doxycycline (DOX), and antimicrobial peptides LL-37, LL-31, Lactoferrin chimera (LFchimera) and Innate Defense Regulator Peptide 1018 (IDR-1018) against Aggregatibacter actinomycetemcomitans ATCC 43718 were determined using colony culturing assay. Subsequently, in vitro activity of the most effective drug and peptide combination was evaluated by checkerboard technique. Impact of the drug and peptide co-administration on biofilm at different stages, i.e., during adhesion and 1-day old biofilm was compared to each of the agents used alone. Results revealed that the killing effects of all AMPs range from 13-100%. In contrast, MH and DOX at 1 and 5 μM showed no killing activity and instead stimulated growth of bacteria. DOX has better killing activity than MH. LFchimera displayed the strongest killing amongst the peptides. Checkerboard technique revealed that combining DOX and LFchimera yielded synergism. Confocal laser scanning microscopy further showed that the combination of DOX and LFchimera caused significant reduction of bacterial adhesion and reduction of biomass, average biofilm thickness and substratum biofilm coverage of 1-day old biofilm compared to DOX and LFchimera alone. In conclusion, LFchimera alone and in combination with DOX exhibited strong antibacterial and anti-biofilm property against A. actinomycetemcomitans. The findings suggest that LFchimera should be considered for development as a new potential therapeutic agent that may be used as an adjunctive treatment for periodontitis.
Topics: Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Biofilms; Drug Synergism; Humans; Lactoferrin; Periodontitis; Plankton; Recombinant Fusion Proteins
PubMed: 31329599
DOI: 10.1371/journal.pone.0217205 -
BMC Oral Health May 2021Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the...
BACKGROUND
Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the microbes using antimicrobial agents. This study determined the ability of Streptococcus salivarius to inhibit IL-6 and IL-8 production by gingival fibroblasts when activated by periodontal pathogens and their effect on the salivary microbiome.
METHODS
Primary human gingival fibroblasts were challenged with Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum and a combination of all three. IL-6 and IL-8 cytokine release were measured. Using this same model, S. salivarius K12, M18 and different supernatant and whole-cell lysate fractions of S. salivarius K12 were administered to pathogen-induced fibroblasts. A patient study of healthy participants was also conducted to determine the effect S. salivarius K12 had on the native microbiome using 16S next generation sequence analysis.
RESULTS
All pathogens tested induced a significant IL-6 and IL-8 response. S. salivarius K12 or M18, did not exhibit an increase in inflammatory cytokines. When either of the probiotic strains were co-administered with a pathogen, there were significant reductions in both IL-6 and IL-8 release. This effect was also observed when gingival fibroblasts were pre-treated with either S. salivarius K12 or M18 and then stimulated with the oral pathogens. Chewing gum containing S. salivarius K12 did not alter the salivary microbiome and did not increase inflammatory markers in the oral cavity.
CONCLUSION
S. salivarius K12 and M18 prevented immune activation induced by periodontal disease pathogens. S. salivarius K12 did not alter the salivary microbiome or induce immune activation when administered as a chewing gum. These results warrant further study to determine if it may be an effective treatment in a model of periodontal disease.
Topics: Aggregatibacter actinomycetemcomitans; Fusobacterium nucleatum; Humans; Periodontal Diseases; Porphyromonas gingivalis; Streptococcus salivarius
PubMed: 33962608
DOI: 10.1186/s12903-021-01606-z -
The Journal of Pharmacy and Pharmacology Mar 2021We and others have previously shown that epigallocatechin gallate (EGCg) inhibits the activity of an important virulence factor, leukotoxin (LtxA), produced by the oral...
OBJECTIVES
We and others have previously shown that epigallocatechin gallate (EGCg) inhibits the activity of an important virulence factor, leukotoxin (LtxA), produced by the oral bacterium Aggregatibacter actinomycetemcomitans, suggesting the potential use of this molecule as an anti-virulence strategy to treat periodontal infections. Here, we sought to better understand the effects of EGCg on toxin secretion and A. actinomycetemcomitans pathogenicity in a co-culture model.
METHODS
We used a quantitative immunoblot assay to determine the concentrations of LtxA in the bacterial supernatant and on the bacterial cell surface. Using a co-culture model, consisting of A. actinomycetemcomitans and THP-1 cells, we studied the impact of EGCg-mediated changes in LtxA secretion on the toxicity of A. actinomycetemcomitans.
KEY FINDINGS
EGCg increased production of LtxA and changed the localization of secreted LtxA from the supernatant to the surface of the bacterial cells. In the co-culture model, a single low dose of EGCg did not protect host THP-1 cells from A. actinomycetemcomitans-mediated cytotoxicity, but a multiple dosing strategy had improved effects.
CONCLUSIONS
Together, these results demonstrate that EGCg has important, but complicated, effects on toxin secretion and activity; new dosing strategies and comprehensive model systems may be required to properly develop these anti-virulence activities.
Topics: Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Bacterial Toxins; Catechin; Coculture Techniques; Dose-Response Relationship, Drug; Exotoxins; Humans; Periodontitis; Virulence
PubMed: 33793838
DOI: 10.1093/jpp/rgaa051 -
International Dental Journal Feb 2024The aim of this work was to explore the association between Aggregatibacter actinomycetemcomitans (A actinomycetemcomitans) infection and disease activity amongst those...
OBJECTIVE
The aim of this work was to explore the association between Aggregatibacter actinomycetemcomitans (A actinomycetemcomitans) infection and disease activity amongst those with rheumatoid arthritis (RA) with or without periodontitis (PD) in a Chinese population.
METHODS
A case-control study was conducted from November 2017 to March 2019. The correlation coefficients between A actinomycetemcomitans positivity and RA-related examination indicators as well as periodontal examination parameters were calculated by using the Spearman correlation analysis.
RESULTS
A total of 115 patients with RA were recruited: 67 patients with RA only and 48 with RA + PD. The percentage of A actinomycetemcomitans positivity was significantly higher in the RA + PD group compared with the RA-only group (P = .007 for positive percentage; P = .020 for percentage of A actinomycetemcomitans positivity in the total oral microbiome). Furthermore, RA-related measures such as Disease Activity Score 28, rheumatoid factor, anticyclic citrullinated peptide, and anticitrullinated protein antibodies were all positively correlated with the percentage of A actinomycetemcomitans positivity (P range: .002∼.041). In addition, significant correlations were observed amongst A actinomycetemcomitans positivity and probing pocket depth (P = .027) and gingival index (P = .043), whereas null correlations were found amongst the percentage of A actinomycetemcomitans positivity and plaque index (P = .344), clinical attachment loss (P = .217), and bleeding on probing (P = .710).
CONCLUSIONS
A actinomycetemcomitans infection may be related to the development of PD amongst patients with RA.
Topics: Humans; Aggregatibacter actinomycetemcomitans; Case-Control Studies; Periodontitis; Arthritis, Rheumatoid; Periodontal Attachment Loss
PubMed: 37517936
DOI: 10.1016/j.identj.2023.06.011 -
International Journal of Molecular... Jan 2023Elevated serum immunoglobulin (Ig) antibody levels are observed in Crohn's disease patients. The aim of this study was to evaluate the salivary IgA and IgG antibody...
Elevated serum immunoglobulin (Ig) antibody levels are observed in Crohn's disease patients. The aim of this study was to evaluate the salivary IgA and IgG antibody levels against , , , and in Crohn's disease patients. Eighty-eight participants (47 Crohn's disease patients and 41 systemically healthy age- and gender-matched controls) were included in the study. Oral and medical health statuses were recorded and salivary samples were collected. Salivary , , , and carriage were analyzed with DNA sequencing technique, salivary levels of IgG1, IgG2, IgG3, IgG4, and IgM were measured with the Luminex xMAP™ technique, and salivary IgA and IgG antibody levels against , , , and were detected by ELISA. As result, higher salivary IgG2 ( = 0.011) and IgG3 ( = 0.006), IgA ( < 0.001), IgG ( = 0.001), and IgG ( < 0.001) antibody levels were detected in the Crohn's disease group compared to the controls. Salivary carriage was lower in the Crohn's disease group in comparison to the controls ( = 0.024). In conclusion, salivary IgA antibody responses against and IgG antibody responses against have independent associations with Crohn's disease.
Topics: Humans; Immunoglobulin G; Antibody Formation; Crohn Disease; Periodontitis; Porphyromonas gingivalis; Immunoglobulin A; Aggregatibacter actinomycetemcomitans; Antibodies, Bacterial
PubMed: 36768711
DOI: 10.3390/ijms24032385 -
Journal of Dental Research Jan 2016Gram-negative facultative Aggregatibacter actinomycetemcomitans is an oral pathogen associated with periodontitis. The genetic heterogeneity among A.... (Comparative Study)
Comparative Study
Gram-negative facultative Aggregatibacter actinomycetemcomitans is an oral pathogen associated with periodontitis. The genetic heterogeneity among A. actinomycetemcomitans strains has been long recognized. This study provides a comprehensive genomic analysis of A. actinomycetemcomitans and the closely related nonpathogenic Aggregatibacter aphrophilus. Whole genome sequencing by Illumina MiSeq platform was performed for 31 A. actinomycetemcomitans and 2 A. aphrophilus strains. Sequence similarity analysis shows a total of 3,220 unique genes across the 2 species, where 1,550 are core genes present in all genomes and 1,670 are variable genes (accessory genes) missing in at least 1 genome. Phylogenetic analysis based on 397 concatenated core genes distinguished A. aphrophilus and A. actinomycetemcomitans. The latter was in turn divided into 5 clades: clade b (serotype b), clade c (serotype c), clade e/f (serotypes e and f), clade a/d (serotypes a and d), and clade e' (serotype e strains). Accessory genes accounted for 14.1% to 23.2% of the A. actinomycetemcomitans genomes, with a majority belonging to the category of poorly characterized by Cluster of Orthologous Groups classification. These accessory genes were often organized into genomic islands (n = 387) with base composition biases, suggesting their acquisitions via horizontal gene transfer. There was a greater degree of similarity in gene content and genomic islands among strains within clades than between clades. Strains of clade e' isolated from human were found to be missing the genomic island that carries genes encoding cytolethal distending toxins. Taken together, the results suggest a pattern of sequential divergence, starting from the separation of A. aphrophilus and A. actinomycetemcomitans through gain and loss of genes and ending with the divergence of the latter species into distinct clades and serotypes. With differing constellations of genes, the A. actinomycetemcomitans clades may have evolved distinct adaptation strategies to the human oral cavity.
Topics: Aggregatibacter actinomycetemcomitans; Aggregatibacter aphrophilus; Bacterial Toxins; Base Composition; DNA, Bacterial; DNA, Concatenated; Evolution, Molecular; Gene Transfer, Horizontal; Genes, Bacterial; Genetic Heterogeneity; Genetic Speciation; Genetic Variation; Genome, Bacterial; Genomic Islands; Humans; Mouth; Phylogeny; Protein Subunits; Sequence Analysis, DNA; Serogroup
PubMed: 26420795
DOI: 10.1177/0022034515608163 -
Frontiers in Cellular and Infection... 2021Periodontitis is a chronic inflammatory gum disease associated with systemic diseases such as cardiovascular diseases.
BACKGROUND
Periodontitis is a chronic inflammatory gum disease associated with systemic diseases such as cardiovascular diseases.
AIM
To investigate the association of systemic blood biomarkers, C-reactive protein (CRP), levels of lipopolysaccharide (LPS), and IgG levels against periodontal pathogens (Aa) and (Pg) with the stability, based on the aortic diameter, the growth rate and the eligibility for surgical intervention, of patients with abdominal aortic aneurysm (AAA).
METHODS
Patients with stable AAA (n = 30) and unstable AAA (n = 31) were recruited. The anti- and anti- IgG levels were analyzed by ELISA, the LPS analysis was performed by using the limulus amebocyte lysate (LAL) test, and plasma levels of CRP were determined using an immune turbidimetric method. The association between these blood systemic biomarkers, AAA features, periodontal clinical parameters and oral microbial profiles were explored. Regression models were used to test the relationship between variables.
RESULTS
The presence of antibodies against Pg and Aa, LPS and high CRP concentrations were found in all AAA patients. The IgG levels were similar in patients with stable and unstable AAA (both for Aa and Pg). Among investigated blood biomarkers, only CRP was associated with AAA stability. The amount of LPS in saliva, supra, and subgingival plaque were significantly associated with the systemic LPS (p <0.05).
CONCLUSIONS
This study emphasizes the presence of antibodies against Pg and Aa, LPS and high CRP concentrations in all AAA patients. The presence of Pg in saliva and subgingival plaque was significantly associated with the blood LPS levels. For further studies investigating periodontitis and systemic diseases, specific predictive blood biomarkers should be considered instead of the use of antibodies alone.
Topics: Aggregatibacter actinomycetemcomitans; Aortic Aneurysm, Abdominal; Biomarkers; Humans; Periodontitis; Porphyromonas gingivalis
PubMed: 35096635
DOI: 10.3389/fcimb.2021.766462