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Archives of Oral Biology Feb 2018To test the hypothesis that virulence genes of Aggregatibacter actinomycetemcomitans can be expressed and confer fitness advantages in the closely related...
OBJECTIVE
To test the hypothesis that virulence genes of Aggregatibacter actinomycetemcomitans can be expressed and confer fitness advantages in the closely related Aggregatibacter aphrophilus.
DESIGN
Clinical isolates of A. aphrophilus were screened for natural competence with marked genomic DNA from A. actinomycetemcomitans and A. aphrophilus. The gene katA of A. actinomycetemcomitans D7S-1 and its flanking regions were constructed and inserted into a comparable locus in the genome of a naturally competent A. aphrophilus strain by a markerless protocol via natural transformation. Mutants of A. actinomycetemcomitans with or without katA were also constructed by a similar protocol. Discs soaked with either 0.03% hydrogen peroxide or broth culture of Streptococcus gordonii Challis were placed on the agar with cultures of A. actinomycetemcomitans or A. aphrophilus. The size of the growth inhibition zone associated with the disc was measured after 2-day culture.
RESULTS
Five of the 13A. aphrophilus strains exhibited a transformation frequency of 10 or higher. The intra- and inter-species transformation frequencies were comparable. The inhibition zones for katA-negative strains of A. actinomycetemcomitans or A. aphrophilus were 3- to 7-fold larger than those associated with katA-positive strains (p<0.05).
CONCLUSIONS
There was no apparent species barrier for the transfer and expression of A. actinomycetemcomitans katA in A. aphrophilus. The inserted A. actinomycetemcomitans-specific katA gene in A. aphrophilus strain NJ8700 conferred resistance to inhibition by hydrogen peroxide or S. gordonii. The potential to swap genes between these two closely related oral species may be an alternative approach for investigating the virulence determinants of A. actinomycetemcomitans.
Topics: Aggregatibacter actinomycetemcomitans; Aggregatibacter aphrophilus; Catalase; Gene Transfer Techniques; Genomic Islands; Genomics; Hydrogen Peroxide; Mutagenesis, Insertional; Polymerase Chain Reaction; Virulence
PubMed: 29223024
DOI: 10.1016/j.archoralbio.2017.12.002 -
Journal of Global Antimicrobial... Sep 2020Administration of systemic antimicrobials as an adjunct to mechanical treatment of periodontitis and sites with adverse clinical results leads to improved outcomes. This...
OBJECTIVES
Administration of systemic antimicrobials as an adjunct to mechanical treatment of periodontitis and sites with adverse clinical results leads to improved outcomes. This study aimed to assess the antimicrobial susceptibility of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia isolated from periodontitis patients to amoxicillin, metronidazole, azithromycin and moxifloxacin.
METHODS
A total of 76 patients diagnosed with generalised periodontitis were included in the study. Subgingival samples were processed by culture. Etest was used to determine susceptibility to amoxicillin, metronidazole, azithromycin and moxifloxacin.
RESULTS
A total of 141 isolates from 76 patients were evaluated, including 61 P. gingivalis, 43 T. forsythia and 37 A. actinomycetemcomitans. Etest results showed complete susceptibility of A. actinomycetemcomitans, P. gingivalis and T. forsythia to moxifloxacin. However, the isolates presented reduced susceptibility to the other antimicrobial agents investigated. Of the A. actinomycetemcomitans isolates, 70.3%, 40.5% and 89.2% were resistant to amoxicillin, azithromycin and metronidazole, respectively. The P. gingivalis samples showed relatively similar rates of resistance to amoxicillin (24.6%), azithromycin (21.3%) and metronidazole (24.6%). Similarly, 25.6%, 21.0% and 25.6% of the T. forsythia isolates were resistant to amoxicillin, azithromycin, and metronidazole, respectively.
CONCLUSION
These findings show that moxifloxacin may be a promising antimicrobial agent against P. gingivalis, T. forsythia and A. actinomycetemcomitans for the treatment of periodontitis. However, amoxicillin, azithromycin and metronidazole were less effective, especially against A. actinomycetemcomitans in vitro.
Topics: Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Humans; Periodontitis; Porphyromonas gingivalis; Tannerella; Tannerella forsythia
PubMed: 32169683
DOI: 10.1016/j.jgar.2020.02.024 -
Frontiers in Cellular and Infection... 2020In order to improve our understanding on the microbial complexity associated with Grade C/molar-incisor pattern periodontitis (GC/MIP), we surveyed the oral and fecal...
In order to improve our understanding on the microbial complexity associated with Grade C/molar-incisor pattern periodontitis (GC/MIP), we surveyed the oral and fecal microbiomes of GC/MIP and compared to non-affected individuals (Control). Seven Afro-descendants with GC/MIP and seven age/race/gender-matched controls were evaluated. Biofilms from supra/subgingival sites (OB) and feces were collected and submitted to sequencing. () JP2 clone genotyping and salivary nitrite levels were determined. Supragingival biofilm of GC/MIP presented greater abundance of opportunistic bacteria. was increased in subgingival healthy sites of GC/MIP compared to Control. and were more abundant whereas was reduced in OB of GC/MIP compared to controls. abundance was 50 times higher in periodontal sites with PD≥ 4 mm of GC/MIP than in controls. GC/MIP oral microbiome was characterized by a reduction in commensals such as , and and enrichment in periodontopathogens, especially and sulfate reducing . The oral microbiome of the JP2-like+ patient was phylogenetically distant from other GC/MIP individuals. GC/MIP presented a higher abundance of sulfidogenic bacteria in the feces, such as , and than controls. These preliminary data show that the dysbiosis of the microbiome in Afro-descendants with GC/MIP was not restricted to affected sites, but was also observed in supragingival and subgingival healthy sites, as well as in the feces. The understanding on differences of the microbiome between healthy and GC/MIP patients will help in developing strategies to improve and monitor periodontal treatment.
Topics: Aggregatibacter actinomycetemcomitans; Desulfovibrio; Erysipelothrix; Feces; Humans; Incisor; Microbiota; Molar; Peptostreptococcus; Periodontitis; RNA, Ribosomal, 16S
PubMed: 33117737
DOI: 10.3389/fcimb.2020.583761 -
Frontiers in Cellular and Infection... 2021The use of systemic antibiotics may influence the oral microbiota composition. Our aim was to investigate in this retrospective study whether the use of prescribed...
The use of systemic antibiotics may influence the oral microbiota composition. Our aim was to investigate in this retrospective study whether the use of prescribed antibiotics associate with periodontal status, oral microbiota, and antibodies against the periodontal pathogens. The Social Insurance Institution of Finland Data provided the data on the use of systemic antibiotics by record linkage to purchased medications and entitled reimbursements up to 1 year before the oral examination and sampling. Six different classes of antibiotics were considered. The Parogene cohort included 505 subjects undergoing coronary angiography with the mean (SD) age of 63.4 (9.2) years and 65% of males. Subgingival plaque samples were analysed using the checkerboard DNA-DNA hybridisation. Serum and saliva antibody levels to periodontal pathogens were analysed with immunoassays and lipopolysaccharide (LPS) activity with the LAL assay. Systemic antibiotics were prescribed for 261 (51.7%) patients during the preceding year. The mean number of prescriptions among them was 2.13 (range 1-12), and 29.4% of the prescriptions were cephalosporins, 25.7% penicillins, 14.3% quinolones, 12.7% macrolides or lincomycin, 12.0% tetracycline, and 5.8% trimethoprim or sulphonamides. In linear regression models adjusted for age, sex, current smoking, and diabetes, number of antibiotic courses associated significantly with low periodontal inflammation burden index (PIBI, < 0.001), bleeding on probing (BOP, = 0.006), and alveolar bone loss (ABL, = 0.042). Cephalosporins associated with all the parameters. The phyla mainly affected by the antibiotics were Bacteroidetes and Spirochaetes. Their levels were inversely associated with the number of prescriptions ( = 0.010 and < 0.001) and directly associated with the time since the last prescription ( = 0.019 and < 0.001). Significant inverse associations were observed between the number of prescriptions and saliva concentrations of , , and and subgingival bacterial amounts of , , , and . Saliva or serum antibody levels did not present an association with the use of antibiotics. Both serum ( = 0.031) and saliva ( = 0.032) LPS activity was lower in patients having any antibiotic course less than 1 month before sampling. Systemic antibiotics have effects on periodontal inflammation and oral microbiota composition, whereas the effects on host immune responses against the periodontal biomarker species seem unchanged.
Topics: Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Biomarkers; Humans; Male; Microbiota; Middle Aged; Porphyromonas gingivalis; Retrospective Studies
PubMed: 35004349
DOI: 10.3389/fcimb.2021.774665 -
Microbiology Spectrum Feb 2023Aggregatibacter actinomycetemcomitans () is a Gram-negative bacterial pathogen associated with periodontitis and nonoral diseases like rheumatoid arthritis and...
Aggregatibacter actinomycetemcomitans () is a Gram-negative bacterial pathogen associated with periodontitis and nonoral diseases like rheumatoid arthritis and Alzheimer´s disease. isolates with the serotypes a, b, and c are globally most prevalent. Importantly, isolates displaying these serotypes have different clinical presentations. While serotype b isolates are predominant in severe periodontitis, serotypes a and c are generally encountered in mild periodontitis or healthy individuals. It is currently unknown how these differences are reflected in the overall secretion of virulence factors. Therefore, this study was aimed at a comparative analysis of exoproteomes from different clinical isolates with serotypes a, b, or c by mass spectrometry, and a subsequent correlation of the recorded exoproteome profiles with virulence. Overall, we identified 425 extracellular proteins. Significant differences in the exoproteome composition of isolates with different serotypes were observed in terms of protein identification and abundance. In particular, serotype a isolates presented more extracellular proteins than serotype b or c isolates. These differences are mirrored in their virulence in infection models based on human salivary gland epithelial cells and neutrophils. Remarkably, serotype a isolates displayed stronger adhesive capabilities and induced more lysis of epithelial cells and neutrophils than serotype b or c isolates. Conversely, serotype c isolates showed relatively low leukotoxicity, while provoking NETosis to similar extents as serotype a and b isolates. Altogether, we conclude that the differential virulence presentation by isolates with the dominant serotypes a, b, or c can be explained by their exoproteome heterogeneity. Periodontitis is an inflammatory disease that causes progressive destruction of alveolar bone and supporting tissues around the teeth, ultimately resulting in tooth loss. The bacterium Aggregatibacter actinomycetemcomitans () is a prevalent causative agent of periodontitis, but this oral pathogen is also associated with serious extraoral diseases like rheumatoid arthritis and Alzheimer's disease. Clinical isolates are usually distinguished by serotyping, because of known serotype-specific differences in virulence. with serotype b is associated with aggressive forms of periodontitis, while isolates with serotypes a or c are usually encountered in cases of mild periodontitis or healthy individuals. The molecular basis for these differences in virulence was so far unknown. In the present study, we pinpoint serotype-specific differences in virulence factor production by clinical isolates. We consider these findings important, because they provide new leads for future preventive or therapeutic approaches to fight periodontitis and associated morbidities.
Topics: Humans; Serogroup; Aggregatibacter actinomycetemcomitans; Virulence; Alzheimer Disease; Periodontitis; Serotyping; Virulence Factors
PubMed: 36541765
DOI: 10.1128/spectrum.03298-22 -
Scientific Reports Jul 2022Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa)...
Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case-control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (≥ 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA.
Topics: Aggregatibacter actinomycetemcomitans; Arthritis, Rheumatoid; Case-Control Studies; Cross-Sectional Studies; Humans; Porphyromonas gingivalis; Smoking
PubMed: 35854051
DOI: 10.1038/s41598-022-16279-z -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2020Periodontal pathogens are the main pathogenic factor of periodontitis. Periodontal pathogens have a large variety of virulence factors such as lipopolysaccharide,... (Review)
Review
Periodontal pathogens are the main pathogenic factor of periodontitis. Periodontal pathogens have a large variety of virulence factors such as lipopolysaccharide, fimbriae and proteases, which enables the pathogens to infect periodontal tissues and stimulate the secretion of inflammatory cytokines, causing chronic systemic inflammation. Periodontal pathogens may invade multiple systems such as the circulatory system, immune system, respiratory system and digestive system to cause systematic diseases. Recent studies have shown that periodontal pathogens may have close relations with systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and cancer. Among the periodontal pathogens, can be found in atherosclerotic plaques to impairing the function of the vascular endothelium; may also increase the level of inflammatory factors such as TNF-α to promote insulin resistance and diabetes. Many of the periodontal pathogens such as , and can be detected in the synovial fluid of rheumatoid arthritis patients, suggesting their involvement in the pathogenesis of rheumatoid arthritis. may cause alterations in the intestinal microbiome in mice and promote the occurrence of intestinal tumors. Herein we review the recent progresses in the relationship between periodontal pathogens and systemic diseases.
Topics: Aggregatibacter actinomycetemcomitans; Animals; Fusobacterium nucleatum; Humans; Insulin Resistance; Periodontitis; Porphyromonas gingivalis; Prevotella intermedia
PubMed: 32897213
DOI: 10.12122/j.issn.1673-4254.2020.05.24 -
International Journal of Molecular... Nov 2015Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A... (Meta-Analysis)
Meta-Analysis Review
Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT) as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. The focused question was: "Is it possible to decrease (at least 3 log steps or 99.9%) or even eliminate bacterial growth by photodynamic therapy in vitro when compared to untreated control groups or control groups treated by placebo?" In general, PDT resulted in a substantial reduction of surviving bacteria. However, not all studies showed the desired reduction or elimination. The ranges of log10-reduction were 0.38 (58%) to a complete eradication (100%) for P. gingivalis, 0.21 (39%) to 100% for A. actinomycetemcomitans and 0.3 (50%) to 100% for F. nucleatum. In conclusion, further and particularly more comparable studies are needed to evaluate if PDT can be clinically successful as an adjuvant in periodontal therapy.
Topics: Aggregatibacter actinomycetemcomitans; Anti-Infective Agents; Fusobacterium nucleatum; Humans; Light; Periodontitis; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Treatment Outcome
PubMed: 26580607
DOI: 10.3390/ijms161126027 -
Indian Journal of Medical Microbiology 2017A. actinomycetemcomitans is prevalent in periodontitis but is found in some periodontally healthy individuals as well. Certain serotypes of the organism have shown to... (Comparative Study)
Comparative Study
BACKGROUND
A. actinomycetemcomitans is prevalent in periodontitis but is found in some periodontally healthy individuals as well. Certain serotypes of the organism have shown to determine severity of the disease. The distribution of serotype and genotype is affected by geographic and ethnic variation. Therefore, the present study was aimed to detect serotypes b & c of A. actinomycetemcomitans and the genotypes and find its correlation with periodontal status.
MATERIALS AND METHODS
A total of 75 subjects (25 aggressive periodontitis, 25 chronic periodontitis and 25 periodontally healthy) in age range of 14-55 yrs were included. Subgingival plaque samples were collected and checked for the presence of A. actinomycetemcomitans. Following isolation of the organism, detection of the serotype b or c was done by multiplex PCR. Genotyping of A. actinomycetemcomitans was done by arbitrarily primed PCR(polymerase chain reaction).
RESULTS
Out of 75 plaque samples, 35(46.66%) tested positive for A. actinomycetemcomitans. Serotype c was detected in 19/35 (54.28%), whereas serotype b alone was not detected in any of the samples. Two samples were positive for both the serotypes (b and c) (5.71%) and 14 (40%) were untypeable. 14 different arbitrarily primed PCR genotypes were obtained among 35 A. actinomycetemcomitans isolates.
CONCLUSION
Serotype c was predominant in periodontally diseased as well as periodontally healthy individuals. An association could be present between genotype - serotype and genotype - periodontal status.
Topics: Adolescent; Adult; Aggregatibacter actinomycetemcomitans; Cross-Sectional Studies; Female; Genotype; Genotyping Techniques; Healthy Volunteers; Humans; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Pasteurellaceae Infections; Periodontal Diseases; Serogroup; Young Adult
PubMed: 29405147
DOI: 10.4103/ijmm.IJMM_17_115 -
Frontiers in Immunology 2022Molar-incisor pattern periodontitis (MIPP) in the absence of significant local risk factors or systemic disease, is a rare, early onset periodontal disease phenotype,...
INTRODUCTION
Molar-incisor pattern periodontitis (MIPP) in the absence of significant local risk factors or systemic disease, is a rare, early onset periodontal disease phenotype, with 0.5% to 2.5% global prevalence. The condition is characterized by impaired neutrophil function and persistent (JP2 clone) infection. The aim of this study was to characterize neutrophil functional responses to JP2 and to investigate the neutrophil receptors involved.
MATERIALS AND METHODS
Neutrophils were obtained from whole blood samples of periodontally healthy and MIPP subjects and incubated with the JP2 clone or a non-JP2 clone of . Bacterial survival was tested by blood agar culture; neutrophil death was tested with propidium iodide and flow cytometry; Reactive oxygen production (ROS) was measured with 2',7'-dichlorofluorescein diacetate and a fluorescence plate reader; the cytokinome was analysed using an array profiler, ELISA and RT-PCR. Receptors binding to JP2 were isolated using a novel immunoprecipitation assay and validated functionally using specific blocking antibodies.
RESULTS
JP2 and non-JP2 survival was comparable between all the neutrophil groups. Resistance to neutrophil necrosis following exposure to JP2 was significantly lower in the MIPP group, than in all the other groups (p<0.0001). Conversely, MIPP neutrophils showed lower levels of ROS production in response to JP2 infection compared with that of healthy neutrophils (p<0.001). Furthermore, significantly lower levels of cytokines, such as IL8, IL10 and TNFα, were observed during JP2 incubation with MIPP neutrophils than upon incubation with periodontally healthy neutrophils. Various proteins expressed on neutrophils bind to JP2. Of these, CD18 was found to mediate neutrophil necrosis. The CD18 receptor on MIPP neutrophils acts differently from that on periodontally healthy patients neutrophils, and appears to reflect differential neutrophil reactions to JP2.
CONCLUSION
This study portrays a fundamental difference in neutrophil response to JP2 infection between periodontally healthy and MIPP patients. This was evident in the resistance to necrosis, and lower ROS and cytokine production, despite the persistent presence of viable JP2. Whilst in periodontally healthy neutrophils, JP2 binds to CD18 on cell surfaces, this is not the case in MIPP neutrophils, suggesting a potential role for CD18 in the periodontal susceptibility of MIPP patients.
Topics: Aggregatibacter actinomycetemcomitans; Clone Cells; Humans; Incisor; Necrosis; Neutrophils; Periodontitis; Reactive Oxygen Species
PubMed: 35663998
DOI: 10.3389/fimmu.2022.847372