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Microbiology Spectrum Feb 2022Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with...
Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with findings that include the O-glycosylation motif, the structure of the O-glycans in a few species, and an extensive O-glycoproteome analysis in Tannerella forsythia. However, O-glycosylation has not yet been confirmed in P. gingivalis. We therefore used glycoproteomics approaches including partial deglycosylation with trifluoromethanesulfonic acid as well as both HILIC and FAIMS based glycopeptide enrichment strategies leading to the identification of 257 putative glycosylation sites in 145 glycoproteins. The sequence of the major O-glycan was elucidated to be HexNAc-HexNAc(P-Gro-[Ac])-dHex-Hex-HexA-Hex(dHex). Western blot analyses of mutants lacking the glycosyltransferases PGN_1134 and PGN_1135 demonstrated their involvement in the biosynthesis of the glycan while mass spectrometry analysis of the truncated O-glycans suggested that PGN_1134 and PGN_1135 transfer the two HexNAc sugars. Interestingly, a strong bias against the O-glycosylation of abundant proteins exposed to the cell surface such as abundant T9SS cargo proteins, surface lipoproteins, and outer membrane β-barrel proteins was observed. In contrast, the great majority of proteins associated with the inner membrane or periplasm were glycosylated irrespective of their abundance. The P. gingivalis O-glycosylation system may therefore function to establish the desired physicochemical properties of the periplasm. Porphyromonas gingivalis is an oral pathogen primarily associated with severe periodontal disease and further associated with rheumatoid arthritis, dementia, cardiovascular disease, and certain cancers. Protein glycosylation can be important for a variety of reasons including protein function, solubility, protease resistance, and thermodynamic stability. This study has for the first time demonstrated the presence of O-linked glycosylation in this organism by determining the basic structure of the O-glycans and identifying 257 glycosylation sites in 145 proteins. It was found that most proteins exposed to the periplasm were O-glycosylated; however, the abundant surface exposed proteins were not. The O-glycans consisted of seven monosaccharides and a glycerol phosphate with 0-2 acetyl groups. These glycans are likely to have a stabilizing role to the proteins that bear them and must be taken into account when the proteins are produced in heterologous organisms.
Topics: Amino Acid Motifs; Bacterial Proteins; Carbohydrate Sequence; Glycoproteins; Glycosylation; Humans; Polysaccharides; Porphyromonas gingivalis
PubMed: 34985300
DOI: 10.1128/spectrum.01502-21 -
Frontiers in Cellular and Infection... 2021Late-onset periodontitis is associated with a series of inflammatory reactions induced by periodontal pathogens, such as , a keystone pathogen involved in periodontitis.... (Review)
Review
Late-onset periodontitis is associated with a series of inflammatory reactions induced by periodontal pathogens, such as , a keystone pathogen involved in periodontitis. Neutrophils are the most abundant leukocytes in the periodontal pocket/gingival crevice and inflamed periodontal tissues. They form a "wall" between the dental plaque and the junctional epithelium, preventing microbial invasion. The balance between neutrophils and the microbial community is essential to periodontal homeostasis. Excessive activation of neutrophils in response to periodontal pathogens can induce tissue damage and lead to periodontitis persistence. Therefore, illuminating the interactions between neutrophils and periodontal pathogens is critical for progress in the field of periodontitis. The present review aimed to summarize the interactions between neutrophils and periodontal pathogens in late-onset periodontitis, including neutrophil recruitment, neutrophil mechanisms to clear the pathogens, and pathogen strategies to evade neutrophil-mediated elimination of bacteria. The recruitment is a multi-step process, including tethering and rolling, adhesion, crawling, and transmigration. Neutrophils clear the pathogens mainly by phagocytosis, respiratory burst responses, degranulation, and neutrophil extracellular trap (NET) formation. The mechanisms that pathogens activate to evade neutrophil-mediated killing include impairing neutrophil recruitment, preventing phagocytosis, uncoupling killing from inflammation, and resistance to ROS, degranulation products, and NETs.
Topics: Extracellular Traps; Humans; Neutrophils; Periodontitis; Phagocytosis; Porphyromonas gingivalis
PubMed: 33777839
DOI: 10.3389/fcimb.2021.627328 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Porphyromonas gingivalis; Immune Evasion; Dysbiosis; Periodontal Diseases
PubMed: 37842000
DOI: 10.3389/fcimb.2023.1289103 -
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 -
Molecular Oral Microbiology Aug 2020Inflammasomes are multiprotein complexes that regulate immune processes in response to infections and tissue damage. They modulate Interleukin-1beta (IL-1β) expression,...
INTRODUCTION
Inflammasomes are multiprotein complexes that regulate immune processes in response to infections and tissue damage. They modulate Interleukin-1beta (IL-1β) expression, a major proinflammatory cytokine. The inflammasome/IL-1β pathway is involved in head and neck squamous cell carcinoma (HNSCC) progression and the periodontal pathogens Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) have been reported to cause chronic inflammation in HNSCC. The aim of this study was to characterise the role of these pathogens in regulating inflammasome activity and the IL-1β response in HNSCC in vitro.
METHODS
An HNSCC cell line (H400) was exposed to Fn and Pg individually or in combination for 24h, ± incubation for 30 min with 5 mM adenosine triphosphate (ATP). Transcript levels of inflammasomes, NLRP3 and AIM2; inflammasome-regulatory proteins, POP1, CARD16 and TRIM16; and inflammasome-component, ASC and caspase 1 and IL-1β, were assayed by RT-PCR. Expression of IL-1β was by immunocytochemistry and ELISA.
RESULTS
NLRP3 expression was significantly upregulated in response to Pg, Fn + Pg, Pg + ATP and Fn + Pg + ATP. AIM2 was significantly upregulated by Fn, Pg and Fn + Pg + ATP exposure. All conditions significantly upregulated IL-1β gene expression. POP1 expression was significantly downregulated by Pg or Fn exposure but not by Fn + Pg. Intracellular pro- and mature IL-1β were significantly higher following Fn and Pg + ATP exposure.
CONCLUSION
Pg alone increased IL-1β by upregulating AIM2, NLRP3 and downregulating POP1. Fn promoted IL-1β by increasing AIM2 and downregulating POP1. Pg + ATP with or without Fn upregulated NLRP3, IL-1β by downregulating POP1. Periodontal pathogens may contribute to HNSCC pathogenesis by increasing the IL-1β response due to inflammasome dysregulation.
Topics: Caspase 1; Fusobacterium nucleatum; Inflammasomes; Interleukin-1beta; NLR Family, Pyrin Domain-Containing 3 Protein; Porphyromonas gingivalis
PubMed: 32516848
DOI: 10.1111/omi.12302 -
Clinical and Experimental Dental... Apr 2023This review was conducted to assess the effectiveness of xylitol against Porphyromonas gingivalis anaerobic species, a key microbe contributing to periodontal disease... (Review)
Review
OBJECTIVE
This review was conducted to assess the effectiveness of xylitol against Porphyromonas gingivalis anaerobic species, a key microbe contributing to periodontal disease pathogenesis.
MATERIAL AND METHODS
Relevant studies published on seven online databases (Cochrane, Ovid, Pubmed, Pubmed Central, Scopus, Google Scholar, and Web of Science) were included in accordance with the PRISMA guidelines. Inclusion criteria allowed all study designs involving xylitol and P. gingivalis, literature published since the year 2000, and all xylitol delivery forms.
RESULTS
The initial search yielded 186 papers. After the removal of duplicates, five reviewers screened every article for eligibility and seven articles were selected for data extraction. Four out of seven included studies assessed the dose-dependent effect of xylitol on P. gingivalis growth, two studies assessed the effect of xylitol on P. gingivalis-induced cytokine expression, and one study assessed both domains.
CONCLUSIONS
From the in vitro studies included in this systematic review, there is some evidence of xylitol's inhibitory effect on P. gingivalis. However, more evidence derived from in vivo studies is required to confirm its effectiveness warranting their routine use.
Topics: Humans; Porphyromonas gingivalis; Xylitol; Periodontal Diseases; Cytokines
PubMed: 36894516
DOI: 10.1002/cre2.724 -
Frontiers in Cellular and Infection... 2023is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. expresses a variety of virulence factors that disrupt innate... (Review)
Review
is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. expresses a variety of virulence factors that disrupt innate and adaptive immunity, allowing to survive and multiply in the host and destroy periodontal tissue. In addition to periodontal disease, is also associated with systemic diseases, of which insulin resistance is an important pathological basis. causes a systemic inflammatory response, disrupts insulin signaling pathways, induces pancreatic β-cell hypofunction and reduced numbers, and causes decreased insulin sensitivity leading to insulin resistance (IR). In this paper, we systematically review the studies on the mechanism of insulin resistance induced by , discuss the association between and systemic diseases based on insulin resistance, and finally propose relevant therapeutic approaches. Overall, through a systematic review of the mechanisms related to systemic diseases caused by through insulin resistance, we hope to provide new insights for future basic research and clinical interventions for related systemic diseases.
Topics: Humans; Porphyromonas gingivalis; Insulin Resistance; Base Composition; RNA, Ribosomal, 16S; Phylogeny; Sequence Analysis, DNA; Insulin
PubMed: 37520442
DOI: 10.3389/fcimb.2023.1209381 -
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 -
Frontiers in Immunology 2022() is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. has recently been detected in rheumatoid... (Review)
Review
() is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer's disease (AD), and the presence of in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages' immune response, in which subsequently promote the diseases' initiation and progression. as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.
Topics: Arthritis, Rheumatoid; Humans; Inflammasomes; Macrophage Activation; Macrophages; Periodontitis; Porphyromonas gingivalis
PubMed: 35967399
DOI: 10.3389/fimmu.2022.952040 -
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