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Molecular Oral Microbiology Aug 2021RagA and RagB proteins are major components of the outer membrane of the oral pathogen Porphyromonas gingivalis and, while recently suggested to represent a novel... (Review)
Review
RagA and RagB proteins are major components of the outer membrane of the oral pathogen Porphyromonas gingivalis and, while recently suggested to represent a novel peptide uptake system, their full function is still under investigation. Herein, we (a) discuss the evidence that the rag locus contributes to P. gingivalis virulence; (b) provide insight to Rag protein potential biological function in macromolecular transport and other aspects of bacterial physiology; (c) address the host response to Rag proteins which are immunodominant and immunomodulatory; and (d) review the potential of Rag-focused therapeutic strategies for the control of periodontal diseases.
Topics: Bacterial Proteins; Humans; Periodontal Diseases; Porphyromonas gingivalis; Virulence
PubMed: 34032024
DOI: 10.1111/omi.12345 -
Frontiers in Immunology 2023Atherosclerosis (AS) is a chronic inflammatory disease, involving a pathological process of endothelial dysfunction, lipid deposition, plaque rupture, and arterial... (Review)
Review
Atherosclerosis (AS) is a chronic inflammatory disease, involving a pathological process of endothelial dysfunction, lipid deposition, plaque rupture, and arterial occlusion, and is one of the leading causes of death in the world population. The progression of AS is closely associated with several inflammatory diseases, among which periodontitis has been shown to increase the risk of AS. (), presenting in large numbers in subgingival plaque biofilms, is the "dominant flora" in periodontitis, and its multiple virulence factors are important in stimulating host immunity. Therefore, it is significant to elucidate the potential mechanism and association between and AS to prevent and treat AS. By summarizing the existing studies, we found that promotes the progression of AS through multiple immune pathways. can escape host immune clearance and, in various forms, circulate with blood and lymph and colonize arterial vessel walls, directly inducing local inflammation in blood vessels. It also induces the production of systemic inflammatory mediators and autoimmune antibodies, disrupts the serum lipid profile, and thus promotes the progression of AS. In this paper, we summarize the recent evidence (including clinical studies and animal studies) on the correlation between and AS, and describe the specific immune mechanisms by which promotes AS progression from three aspects (immune escape, blood circulation, and lymphatic circulation), providing new insights into the prevention and treatment of AS by suppressing periodontal pathogenic bacteria.
Topics: Animals; Porphyromonas gingivalis; Periodontitis; Inflammation; Atherosclerosis; Lipids
PubMed: 36999040
DOI: 10.3389/fimmu.2023.1103592 -
Frontiers in Cellular and Infection... 2022The association between periodontal disease and systemic disease has become a research hotspot. (), a crucial periodontal pathogen, affects the development of systemic... (Review)
Review
The association between periodontal disease and systemic disease has become a research hotspot. (), a crucial periodontal pathogen, affects the development of systemic diseases. The pathogenicity of is largely linked to interference with the host's immunity. This review aims to discover the role of in the modulation of the host's adaptive immune system through a large number of virulence factors and the manipulation of cellular immunological responses (mainly mediated by T cells). These factors may affect the cause of large numbers of systemic diseases, such as atherosclerosis, hypertension, adverse pregnancy outcomes, inflammatory bowel disease, diabetes mellitus, non-alcoholic fatty liver disease, rheumatoid arthritis, and Alzheimer's disease. The point of view of adaptive immunity may provide a new idea for treating periodontitis and related systemic diseases.
Topics: Female; Pregnancy; Humans; Porphyromonas gingivalis; Immunity, Cellular; Periodontal Diseases; Adaptive Immunity; Alzheimer Disease
PubMed: 36467726
DOI: 10.3389/fcimb.2022.1026457 -
Biomedical Journal Aug 2016Despite recent advances unraveling mechanisms of host-pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven... (Review)
Review
Despite recent advances unraveling mechanisms of host-pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven inflammation remains an emerging research field with many unanswered questions. As one of the most-studied oral pathogens, Porphyromonas gingivalis is considered as a keystone pathogen with a central role in development of periodontal disease. This pathogen needs to evade immune-mediated defense mechanisms and tolerate inflammation in order to survive in the host. In this review, we summarize evidence showing that purinergic signaling modulates P. gingivalis survival and cellular immune responses, and discuss the role played by inflammasome activation and cell death during P. gingivalis infection.
Topics: Humans; Immunity, Innate; Inflammasomes; Inflammation; Porphyromonas gingivalis; Signal Transduction
PubMed: 27793267
DOI: 10.1016/j.bj.2016.08.003 -
Future Microbiology 2015Porphyromonas gingivalis is one of the keystone pathogens associated with chronic periodontitis. All P. gingivalis strains examined thus far produce outer membrane... (Review)
Review
Porphyromonas gingivalis is one of the keystone pathogens associated with chronic periodontitis. All P. gingivalis strains examined thus far produce outer membrane vesicles. Recent studies have found that vesicles possess some well-known virulence factors of P. gingivalis such as adhesins, toxins and proteolytic enzymes. Carrying most of the characteristic features of their parent P. gingivalis cells, vesicles communicate with host cells and other members of microbial biofilms, resulting in the transmission of virulence factors into these host cells and the formation of pathogenic bacteria-dominated microbial communities. An in-depth understanding of both the nature and role of vesicles in the pathogenicity of P. gingivalis is both important and timely, particularly when speaking of periodontitis and its related systemic effects.
Topics: Adhesins, Bacterial; Biofilms; Humans; Microbial Consortia; Organelle Biogenesis; Periodontitis; Porphyromonas gingivalis; Transport Vesicles; Virulence Factors
PubMed: 26343879
DOI: 10.2217/fmb.15.63 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Porphyromonas gingivalis; Immune Evasion; Dysbiosis; Periodontal Diseases
PubMed: 37842000
DOI: 10.3389/fcimb.2023.1289103 -
Journal of Integrative Neuroscience Aug 2023Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis...
BACKGROUND
Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from (), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions.
MATERIALS AND METHODS
Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and -lipopolysaccharide (-LPS) injection protocols. The rats received an intraperitoneal injection of saline or -LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas.
RESULTS
The FST immobility time in the -LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the -LPS group compared to the sham group. The peripheral administration of -LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. -LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3.
CONCLUSIONS
The major result of this study is that a repeated systemic administration of -LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Lipopolysaccharides; Porphyromonas gingivalis; Depressive Disorder, Major; Hippocampus
PubMed: 37735127
DOI: 10.31083/j.jin2205120 -
Trends in Microbiology Jan 2021Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of... (Review)
Review
Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of periodontitis. Transposon sequencing has been employed to define the core essential genome of this bacterium and genes conditionally essential in multiple environments - abscess formation; epithelial colonization; and cigarette smoke toxin exposure; as well as to elucidate genes required for iron acquisition and a functional type 9 secretion system. Validated and predicted protein catabolism genes identified include a combination of established virulence factors and a larger set of seemingly more mundane proteolytic genes. The functions and relevance of genes that share essentiality in multiple disease-relevant conditions are examined. These common stress-related genes may represent particularly attractive therapeutic targets for the control of P. gingivalis infections.
Topics: Animals; Bacterial Proteins; Bacteroidaceae Infections; Genes, Essential; Humans; Porphyromonas gingivalis; Virulence Factors
PubMed: 33071035
DOI: 10.1016/j.tim.2020.09.002 -
European Journal of Clinical... Nov 2020Porphyromonas gingivalis, a major subgingival plaque bacterium in periodontitis, has recently attracted much attention as a possible microbial driver in Alzheimer's... (Review)
Review
Porphyromonas gingivalis, a major subgingival plaque bacterium in periodontitis, has recently attracted much attention as a possible microbial driver in Alzheimer's disease. In the present paper, another common neuroinflammatory disease, Parkinson's disease (PD), is discussed. A recent study found major virulence factors of P. gingivalis such as gingipain R1 (RgpA) and lipopolysaccharide in the blood circulation of a PD population. The current review reveals how features such as systemic inflammation, hypercoagulation, presence of amyloid fibrin(ogen) in plasma, and marked ultrastructural changes in platelets, probably induced by P. gingivalis, may affect the development of PD. Several other clinical studies have also demonstrated an association between periodontitis and PD. Even if the risk of periodontal diseases causing neurological disorders needs to be better substantiated, that should not keep us from trying to prevent them by performing careful daily dental hygiene.
Topics: Humans; Parkinson Disease; Porphyromonas gingivalis; Virulence Factors
PubMed: 32564247
DOI: 10.1007/s10096-020-03944-2 -
Frontiers in Cellular and Infection... 2021Apical periodontitis is an inflammatory disease of microbial etiology. It has been suggested that endodontic bacterial DNA might translocate to distant organs blood...
Apical periodontitis is an inflammatory disease of microbial etiology. It has been suggested that endodontic bacterial DNA might translocate to distant organs blood vessels, but no studies have been conducted. We aimed first to explore overall extraradicular infection, as well as specifically by spp; and their potential to translocate from infected root canals to blood through peripheral blood mononuclear cells. In this cross-sectional study, healthy individuals with and without a diagnosis of apical periodontitis with an associated apical lesion of endodontic origin (both, symptomatic and asymptomatic) were included. Apical lesions (N=64) were collected from volunteers with an indication of tooth extraction. Intracanal samples (N=39) and respective peripheral blood mononuclear cells from apical periodontitis (n=14) individuals with an indication of endodontic treatment, as well as from healthy individuals (n=14) were collected. The detection frequencies and loads (DNA copies/mg or DNA copies/μL) of total bacteria, and were measured by qPCR. In apical lesions, the detection frequencies (%) and median bacterial loads (DNA copies/mg) respectively were 70.8% and 4521.6 for total bacteria; 21.5% and 1789.7 for and 18.4% and 1493.9 for . In intracanal exudates, the detection frequencies and median bacterial loads respectively were 100% and 21089.2 (DNA copies/μL) for total bacteria, 41% and 8263.9 for ; and 20.5%, median 12538.9 for Finally, bacteria were detected in all samples of peripheral blood mononuclear cells including apical periodontitis and healthy groups, though total bacterial loads (median DNA copies/μL) were significantly higher in apical periodontitis (953.6) compared to controls (300.7), p<0.05. was equally detected in both groups (50%), but its bacterial load tended to be higher in apical periodontitis (262.3) than controls (158.8), p>0.05; was not detected. Bacteria and specifically spp. were frequently detected in endodontic canals and apical lesions. Also, total bacteria and DNA were detected in peripheral blood mononuclear cells, supporting their plausible role in bacterial systemic translocation.
Topics: Bacterial Translocation; Cross-Sectional Studies; DNA, Bacterial; Humans; Leukocytes, Mononuclear; Periapical Periodontitis; Porphyromonas endodontalis
PubMed: 33816354
DOI: 10.3389/fcimb.2021.649925