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.
Aggregatibacter actinomycetemcomitans ; Animals ; Fusobacterium nucleatum ; Humans ; Insulin Resistance ; Periodontitis ; Porphyromonas gingivalis ; Prevotella intermedia

Phagocytosis is a fundamental process in which phagocytes capture and ingest foreign particles including pathogenic bacteria. Several oral pathogens have anti-phagocytic strategies, which allow them to escape from and survive in phagocytes. Impaired bacteria phagocytosis increases inflammation and contributes to inflammatory diseases. The purpose of this study is to investigate the influences of various agents on oral pathogenic phagocytosis. To determine phagocytosis, Streptococcus mutans, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were stained with 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE), and was measured using flowcytometery and confocal microscopy. The influencing factors on phagocytosis were evaluated through the pretreatment of ROS inhibitor (N-acetyl-L-cysteine (NAC)), lysozyme, potassium chloride (KCI) and adenosine triphosphate (ATP) in THP-1 cells. Expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA). The phagocytosis of various bacteria increased in a MOI-dependent manner. Among the tested bacteria, phagocytosis of P. gingivalis showed the highest fluorescent intensity at same infection time. Among the tested inhibitors, the NAC treatment significantly inhibited phagocytosis in all tested bacteria. In addition, NAC treatment indicated a similar pattern under the confocal microscopy. Moreover, NAC treatment significantly increased the bacteria-induced secretion of IL-1β among the tested inhibitors. Taken together, we conclude that the phagocytosis occurs differently depending on each bacterium. Down-regulation by ROS production inhibited phagocytosis and lead increased of oral pathogens-associated inflammation.
Adenosine Triphosphate ; Aggregatibacter actinomycetemcomitans ; Bacteria ; Cytokines ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Fusobacterium nucleatum ; Inflammation ; Macrophages ; Microscopy, Confocal ; Monocytes ; Muramidase ; Phagocytes ; Phagocytosis ; Porphyromonas gingivalis ; Potassium Chloride ; Streptococcus mutans ; United Nations

PURPOSE: Few studies have examined periodontal pathogens from saliva samples in periodontally healthy young adults. The purposes of this study were to determine the prevalence of periodontopathic bacteria and to quantify periodontal pathogens in saliva samples using real-time polymerase chain reaction (PCR) assays in periodontally healthy Korean young adults under 35 years of age. METHODS: Nine major periodontal pathogens were analyzed by real-time PCR in saliva from 94 periodontally healthy young adults. Quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, Peptostreptococcus anaerobius, and Eikenella corrodens was performed by DNA copy number measurement. RESULTS: F. nucleatum and E. corrodens were detected in all subjects; the numbers of positive samples were 87 (92.6%), 91 (96.8%), and 90 (95.7%) for P. gingivalis, P. anaerobius, and C. rectus, respectively. Other pathogens were also detected in periodontally healthy subjects. Analysis of DNA copy numbers revealed that the most abundant periodontal pathogen was F. nucleatum, which was significantly more prevalent than all other bacteria (P < 0.001), followed by P. anaerobius, P. gingivalis, E. corrodens, C. rectus, and T. denticola. There was no significant difference in the prevalence of each bacterium between men and women. The DNA copy number of total bacteria was significantly higher in men than in women. CONCLUSIONS: Major periodontal pathogens were prevalent in the saliva of periodontally healthy Korean young adults. Therefore, we suggest that the development of periodontal disease should not be overlooked in periodontally healthy young people, as it can arise due to periodontal pathogen imbalance and host susceptibility.
Aggregatibacter actinomycetemcomitans ; Bacteria ; Bacterial Load ; Campylobacter rectus ; Chronic Periodontitis ; DNA ; Eikenella corrodens ; Female ; Forsythia ; Fusobacterium nucleatum ; Healthy Volunteers ; Humans ; Male ; Peptostreptococcus ; Periodontal Diseases ; Porphyromonas gingivalis ; Prevalence ; Prevotella intermedia ; Real-Time Polymerase Chain Reaction ; Saliva ; Treponema denticola ; Young Adult

BACKGROUND: Periodontitis is an inflammatory disease characterized by the breakdown of tooth-supporting tissues, leading to tooth loss. Aggregatibacter actinomycetemcomitans are major etiologic bacterium causing aggressive periodontitis. Ursodeoxycholic acid (UDCA), a hydrophilic gall bladder acid, has been used as an effective drug for various diseases related to immunity. The aim of this study was to investigate the effect of UDCA on the inflammatory response induced by A. actinomycetemcomitans. METHODS: A human acute monocytic leukemia cell line (THP-1) was differentiated to macrophage- like cells by treatment with phorbol 12-mystristate 13-acetate (PMA) and used for all experiments. The cytotoxic effect of UDCA was examined by MTT assay. THP-1 cells were pretreated with UDCA for 30 min before A. actinomycetemcomitans infection and the culture supernatant was analyzed for various cytokine production by ELISA. The effect of UDCA on bacterial growth was examined by measuring optical densities using a spectrophotometer. RESULTS: UDCA showed no cytotoxic effect on THP-1 cells, up to 80 µM Ed highlight: Please confirm technical meaning. UDCA pretreatment inhibited the A. actinomycetemcomitans-induced IL-1β, TNF-α, and IL-17A secretion in a dosedependent manner. UDCA also inhibited IL-21 production at 60 µM. The production of IL-12 and IL-4 was not influenced by A. actinomycetemcomitans infection. CONCLUSION: These findings indicate that UDCA inhibits the production of inflammatory cytokines involved in innate and Th17 immune responses in A. actinomycetemcomitans-infected THP-1-derived macrophages, which suggests its possible use for the control of aggressive periodontitis.
Aggregatibacter actinomycetemcomitans* ; Aggregatibacter* ; Aggressive Periodontitis ; Cell Line ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-12 ; Interleukin-17 ; Interleukin-4 ; Leukemia, Monocytic, Acute ; Macrophages ; Periodontitis ; Tooth Loss ; Urinary Bladder ; Ursodeoxycholic Acid*

OBJECTIVE: Microbial aggregation around dental implants can lead to loss/loosening of the implants. This study was aimed at surface treating titanium microimplants with silver nanoparticles (AgNPs) to achieve antibacterial properties. METHODS: AgNP-modified titanium microimplants (Ti-nAg) were prepared using two methods. The first method involved coating the microimplants with regular AgNPs (Ti-AgNP) and the second involved coating them with a AgNP-coated biopolymer (Ti-BP-AgNP). The topologies, microstructures, and chemical compositions of the surfaces of the Ti-nAg were characterized by scanning electron microscopy (SEM) equipped with energy-dispersive spectrometer (EDS) and X-ray photoelectron spectroscopy (XPS). Disk diffusion tests using Streptococcus mutans, Streptococcus sanguinis, and Aggregatibacter actinomycetemcomitans were performed to test the antibacterial activity of the Ti-nAg microimplants. RESULTS: SEM revealed that only a meager amount of AgNPs was sparsely deposited on the Ti-AgNP surface with the first method, while a layer of AgNP-coated biopolymer extended along the Ti-BP-AgNP surface in the second method. The diameters of the coated nanoparticles were in the range of 10 to 30 nm. EDS revealed 1.05 atomic % of Ag on the surface of the Ti-AgNP and an astounding 21.2 atomic % on the surface of the Ti-BP-AgNP. XPS confirmed the metallic state of silver on the Ti-BP-AgNP surface. After 24 hours of incubation, clear zones of inhibition were seen around the Ti-BP-AgNP microimplants in all three test bacterial culture plates, whereas no antibacterial effect was observed with the Ti-AgNP microimplants. CONCLUSIONS: Titanium microimplants modified with Ti-BP-AgNP exhibit excellent antibacterial properties, making them a promising implantable biomaterial.
Aggregatibacter actinomycetemcomitans ; Biopolymers ; Dental Implants ; Diffusion ; Methods ; Microscopy, Electron, Scanning ; Nanoparticles* ; Photoelectron Spectroscopy ; Silver* ; Streptococcus ; Streptococcus mutans ; Titanium

HACEK is a rare cause of prosthetic valve endocarditis (PVE). We describe 42-year-old male patient who presented with Aggregatibacter aphrophilus PVE and cerebral infarct. A. aphrophilus was isolated from his blood cultures as the sole pathogen, which was confirmed by subsequent 16S rRNA sequencing. He was treated with valve replacement surgery and an 8 week course of pathogen-directed antibiotic therapy and followed for 20 months without recurrence.
Adult ; Aggregatibacter aphrophilus ; Endocarditis* ; Heart Valve Prosthesis ; Humans ; Male ; Recurrence

OBJECTIVETo explore the role of platelet-activating factor receptor (PAFR) in adhesion and invasion of phospho- rylcholine (PC)-positive Aggregatibacter actinomycetemcomitans in cultured human umbilical vein endothelial cells (HUVEC).

METHDOSCultured HUVECs were pretreated with the PAFR antagonist CV3988 or anti-human PAFR monoclonal antibody for 30 min before infection with PC-positive or -negative A. actinomycetemcomitans strains. The bacterial adhesion and invasion and cytotoxicity in the cells were examined using MTT assay.

RESULTSPretreatment with PAFR antagonists at 100, 200 and 500 nmol/L significantly reduced the adhesion rate (36.29∓3.52)%, (19.04∓3.35)% and (7.69∓3.19%), respectively] and invasion rate [(12.12∓1.58)%, (7.08∓0.29)% and (2.60∓2.26)%, respectively] of PC-positive A.actinomycetemcomitans in HUVECs. Similarly, pretreatment with anti-PAFR antibody also significantly reduced A.actinomycetemcomitans adhesion and invasion in HUVECs [(50.05∓5.28)% and (39.09∓6.50)%, respectively]. Pretreatment with PAFR antagonist (200 and 500 nmol/L) and anti-PAFR antibody (25 µg/mL) significantly increased the viability of HUVECs incubated with PC-positive A.actinomycetemcomitans from (25.39∓9.33)% to (91.12∓3.14)%, (94.12∓2.15)% and (65.5∓1.87)%, respectively, but such pretreatments did not increase the viability of cells incubated with PC-negative A.actinomycetemcomitans.

CONCLUSIONSPAFR plays an important role in the adhesion, invasion, and cytotoxicity of PC-positive A.actinomycetemcomitans in cultured HUVECs.

Aggregatibacter actinomycetemcomitans ; pathogenicity ; Bacterial Adhesion ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; microbiology ; Humans ; Platelet Membrane Glycoproteins ; metabolism ; Receptors, G-Protein-Coupled ; metabolism

The aim of this study was to identify the non-Aggregatibacter actinomycetemcomitans bacteria grown on the tryptic soy-serum-bacitracin-vancomycin (TSBV) medium, an A. actinomycetemcomitans selective medium. A total of 82 unidentified bacterial isolates from the oral cavities of a Korean population were kindly provide by the Korean Collection for Oral Microbiology. All the clinical isolates were grown on TSBV medium and bacterial DNA purified from each isolate was subjected to PCR with universal primers specific for bacterial 16S rRNA genes (16S rDNAs) sequence. The each bacterial 16S rDNA was amplified by PCR and the nucleotide sequences of it was determined by the dideoxynucleotide chain termination method. They were identified by 16S rDNA sequence comparison method at the specie-level. The data showed that Neisseria spp. (42 strains), Fusobacterium spp. (10 strains), Capnocytophaga spp. (8 strains), Propionibacterium acnes (5 strains), Aggregatibacter aprophilus (4 strains), Campylobacter spp. (5 strains), Veillonella dispar (3 strains), Streptococcus sp. (1 strain), Haemophilus parainfluenzae (1 strain), Leptotrichia wadei (1 strain), Morococcus sp./Neisseria sp. (1 strain), and Staphylococcus sp. (1 strain) were identified. These results could be used to develop a new A. actinomycetemcomitans-selective medium which is more effective than the TSBV medium in future studies.
Aggregatibacter ; Bacteria* ; Base Sequence ; Campylobacter ; Capnocytophaga ; DNA, Bacterial ; DNA, Ribosomal ; Fusobacterium ; Genes, rRNA ; Haemophilus parainfluenzae ; Leptotrichia ; Methods ; Neisseria ; Polymerase Chain Reaction ; Propionibacterium acnes ; Staphylococcus ; Streptococcus ; Veillonella

PURPOSE: Elderly people are thought to be more susceptible to periodontal disease due to reduced immune function associated with aging. However, little information is available on the nature of immune responses against putative periodontal pathogens in geriatric patients. The purpose of this study was to evaluate the serum IgG antibody responses to six periodontal pathogens in geriatric subjects. METHODS: The study population consisted of 85 geriatric patients and was divided into three groups: 29 mild (MCP), 27 moderate (MoCP) and 29 severe (SCP) chronic periodontitis patients. Serum levels of IgG antibody to Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Prevotella intermedia were measured by enzyme-linked immunosorbent assay (ELISA) and compared among the groups. RESULTS: All three groups showed levels of serum IgG in response to P. gingivalis, A. actinomycetemcomitans, and P. intermedia that were three to four times higher than levels of IgG to T. forsythia, T. denticola, and F. nucleatum. There were no significant differences among all three groups in IgG response to P. gingivalis (P=0.065), T. forsythia (P=0.057), T. denticola (P=0.1), and P. intermedia (P=0.167), although the IgG levels tended to be higher in patients with SCP than in those with MCP or MoCP (with the exception of those for P. intermedia). In contrast, there were significant differences among the groups in IgG levels in response to F. nucleatum (P=0.001) and A. actinomycetemcomitans (P=0.003). IgG levels to A. actinomycetemcomitans were higher in patients with MCP than in those with MoCP or SCP. CONCLUSIONS: When IgG levels were compared among three periodontal disease groups, only IgG levels to F. nucleatum significantly increased with the severity of disease. On the contrary, IgG levels to A. actinomycetemcomitans decreased significantly in patients with SCP compared to those with MCP. There were no significant differences in the IgG levels for P. gingivalis, T. forsythia, T. denticola, and P. intermedia among geriatric patients with chronic periodontitis.
Aged* ; Aggregatibacter actinomycetemcomitans ; Aging ; Antibody Formation ; Chronic Periodontitis ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Forsythia ; Fusobacterium nucleatum ; Geriatrics ; Humans ; Immunity, Humoral* ; Immunoglobulin G ; Periodontal Diseases ; Porphyromonas gingivalis ; Prevotella intermedia ; Treponema denticola

Minimal inhibitory concentration (MIC) is the lowest concentration of antibiotics that inhibits the visible growth of bacteria. It has been reported that sub-MIC of antibiotics may result in morphological alterations, along with the biochemical and physiological changes in bacteria. The purpose of this study was to examine morphological changes of Aggregatibacter actinomycetemcomitans, after the treatment with sub-MIC metronidazole and penicillin. The bacterial morphology was observed with scanning electron microscope, after incubating with sub-MIC antibiotics. The length of A. actinomycetemcomitans was increased after the incubation with sub-MIC metronidazole and penicillin. Sub-MIC metronidazole and penicillin inhibited bacterial division and induced long filaments. Our study showed that metronidazole and penicillin can induce the morphological changes in A. actinomycetemcomitans.
Aggregatibacter actinomycetemcomitans* ; Anti-Bacterial Agents ; Bacteria ; Metronidazole* ; Microscopy, Electron, Scanning* ; Penicillins*