Porphyromonas gingivalis: keeping the pathos out of the biont

The primary goal of the human microbiome initiative has been to increase our understanding of the structure and function of our indigenous microbiota and their effects on human health and predisposition to disease. Because of its clinical importance and accessibility for in vivo study, the oral biofilm is one of the best-understood microbial communities associated with the human body. Studies have shown that there is a succession of select microbial interactions that directs the maturation of a defined community structure, generating the formation of dental plaque. Although the initiating factors that lead to disease development are not clearly defined, in many individuals there is a fundamental shift from a health-associated biofilm community to one that is pathogenic in nature and a central player in the pathogenic potential of this community is the presence of Porphyromonas gingivalis. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions, which is attributed to its arsenal of specialized virulence factors. Hence, this organism is regarded as a primary etiologic agent of periodontal disease progression. In this review, we summarize some of the latest information regarding what is known about its role in periodontitis, including pathogenic potential as well as ecological and nutritional parameters that may shift this commensal to a virulent state. We also discuss parallels between the development of pathogenic biofilms and the human cellular communities that lead to cancer, specifically we frame our viewpoint in the context of ‘wounds that fail to heal’.

[1]  R. Mumper,et al.  Antibacterial effects of blackberry extract target periodontopathogens. , 2013, Journal of periodontal research.

[2]  C. Romano Carratelli,et al.  Effect of resveratrol and modulation of cytokine production on human periodontal ligament cells. , 2012, Cytokine.

[3]  I. Tirosh,et al.  CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome , 2012, Genome research.

[4]  S. Quake,et al.  Quantitative Analysis of the Human Airway Microbial Ecology Reveals a Pervasive Signature for Cystic Fibrosis , 2012, Science Translational Medicine.

[5]  C. J. Wright,et al.  Proteomics of Streptococcus gordonii within a model developing oral microbial community , 2012, BMC Microbiology.

[6]  G. Hajishengallis,et al.  The keystone-pathogen hypothesis , 2012, Nature Reviews Microbiology.

[7]  D. Relman,et al.  Comparisons of clustered regularly interspaced short palindromic repeats and viromes in human saliva reveal bacterial adaptations to salivary viruses. , 2012, Environmental microbiology.

[8]  G. Prendergast,et al.  Amino acid catabolism: a pivotal regulator of innate and adaptive immunity , 2012, Immunological reviews.

[9]  P. Veith,et al.  Differential proteomic analysis of a polymicrobial biofilm. , 2012, Journal of proteome research.

[10]  B. Heitmann,et al.  Intake of dairy calcium and tooth loss among adult Danish men and women. , 2012, Nutrition.

[11]  Haixu Tang,et al.  Diverse CRISPRs Evolving in Human Microbiomes , 2012, PLoS genetics.

[12]  X. Ren,et al.  Amino Acid Metabolism Related to Immune Tolerance by MDSCs , 2012, International reviews of immunology.

[13]  C. Drake,et al.  Current status of immunological approaches for the treatment of prostate cancer , 2012, Current opinion in urology.

[14]  W. Crielaard,et al.  Functional foods/ingredients and periodontal diseases , 2012, European Journal of Nutrition.

[15]  Ruslan Medzhitov,et al.  Disease Tolerance as a Defense Strategy , 2012, Science.

[16]  C. Drake,et al.  Immunotherapy earns its spot in the ranks of cancer therapy , 2012, The Journal of experimental medicine.

[17]  Ana E. Duran-Pinedo,et al.  Effect of Periodontal Pathogens on the Metatranscriptome of a Healthy Multispecies Biofilm Model , 2012, Journal of bacteriology.

[18]  Xuedong Zhou,et al.  The Influence of Iron Availability on Human Salivary Microbial Community Composition , 2012, Microbial Ecology.

[19]  Heidi B. Kaplan,et al.  Natural Competence Is a Major Mechanism for Horizontal DNA Transfer in the Oral Pathogen Porphyromonas gingivalis , 2012, mBio.

[20]  C. Taylor,et al.  Hypoxia Increases Antibiotic Resistance in Pseudomonas aeruginosa through Altering the Composition of Multidrug Efflux Pumps , 2012, Antimicrobial Agents and Chemotherapy.

[21]  P. Veith,et al.  Lactoferrin Inhibits Porphyromonas gingivalis Proteinases and Has Sustained Biofilm Inhibitory Activity , 2012, Antimicrobial Agents and Chemotherapy.

[22]  George Coukos,et al.  Cancer immunotherapy comes of age , 2011, Nature.

[23]  D. Relman,et al.  Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome , 2011, The ISME Journal.

[24]  John D Lambris,et al.  Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. , 2011, Cell host & microbe.

[25]  R. Barrangou,et al.  CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation. , 2011, Annual review of genetics.

[26]  G. Coukos,et al.  The parallel lives of angiogenesis and immunosuppression: cancer and other tales , 2011, Nature Reviews Immunology.

[27]  S. Mazmanian,et al.  Pathobionts of the gastrointestinal microbiota and inflammatory disease. , 2011, Current opinion in immunology.

[28]  S. Gaffen,et al.  TLR2 Signaling and Th2 Responses Drive Tannerella forsythia-Induced Periodontal Bone Loss , 2011, The Journal of Immunology.

[29]  T. Cramer,et al.  Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. , 2011, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[30]  S. Michalek,et al.  TLR4 Signaling via MyD88 and TRIF Differentially Shape the CD4+ T Cell Response to Porphyromonas gingivalis Hemagglutinin B , 2011, The Journal of Immunology.

[31]  Robert H. Austin,et al.  An analogy between the evolution of drug resistance in bacterial communities and malignant tissues , 2011, Nature Reviews Cancer.

[32]  R. Ellen,et al.  New insights into the emerging role of oral spirochaetes in periodontal disease. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[33]  R. Schreiber,et al.  Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion , 2011, Science.

[34]  D. Grenier,et al.  Proteases of Porphyromonas gingivalis as important virulence factors in periodontal disease and potential targets for plant-derived compounds: a review article. , 2011, Current drug targets.

[35]  R. Darveau,et al.  Microbial shift and periodontitis. , 2011, Periodontology 2000.

[36]  T. Padhya,et al.  HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment , 2010, The Journal of experimental medicine.

[37]  J. Izard,et al.  The Human Oral Microbiome , 2010, Journal of bacteriology.

[38]  R. Darveau,et al.  Periodontitis: a polymicrobial disruption of host homeostasis , 2010, Nature Reviews Microbiology.

[39]  T. Matsuo,et al.  Catechins inhibit CXCL10 production from oncostatin M-stimulated human gingival fibroblasts. , 2010, The Journal of nutritional biochemistry.

[40]  J. Slots Human viruses in periodontitis. , 2010, Periodontology 2000.

[41]  Eoin L. Brodie,et al.  Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa. , 2010, Environmental microbiology.

[42]  S. Mazmanian,et al.  A pathobiont of the microbiota balances host colonization and intestinal inflammation. , 2010, Cell host & microbe.

[43]  C. D. Long,et al.  Bacterial diversity in the oral cavity of 10 healthy individuals , 2010, The ISME Journal.

[44]  J. Lewis Metal uptake in host-pathogen interactions: role of iron in Porphyromonas gingivalis interactions with host organisms. , 2010, Periodontology 2000.

[45]  T. Matsuo,et al.  Catechins Inhibit CCL20 Production in IL-17A-Stimulated Human Gingival Fibroblasts , 2009, Cellular Physiology and Biochemistry.

[46]  Forest Rohwer,et al.  Metagenomic Analysis of Respiratory Tract DNA Viral Communities in Cystic Fibrosis and Non-Cystic Fibrosis Individuals , 2009, PloS one.

[47]  B. Stitt,et al.  Expression of peptidylarginine deiminase from Porphyromonas gingivalis in Escherichia coli: enzyme purification and characterization. , 2009, Archives of biochemistry and biophysics.

[48]  C. Scully,et al.  Polyphenols, oral health and disease: A review. , 2009, Journal of dentistry.

[49]  I. N. Rôças,et al.  Community as the unit of pathogenicity: an emerging concept as to the microbial pathogenesis of apical periodontitis. , 2009, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[50]  Jan R. van der Ploeg,et al.  Analysis of CRISPR in Streptococcus mutans suggests frequent occurrence of acquired immunity against infection by M102-like bacteriophages. , 2009 .

[51]  R. Lamont,et al.  Proteomics of Porphyromonas gingivalis within a model oral microbial community , 2009, BMC Microbiology.

[52]  F. Rohwer,et al.  Viruses manipulate the marine environment , 2009, Nature.

[53]  G. R. Persson,et al.  The impact of the stone age diet on gingival conditions in the absence of oral hygiene. , 2009, Journal of periodontology.

[54]  S. Mazmanian,et al.  The gut microbiota shapes intestinal immune responses during health and disease , 2009, Nature Reviews Immunology.

[55]  Viktoria Hancock,et al.  Inactivation of Efflux Pumps Abolishes Bacterial Biofilm Formation , 2008, Applied and Environmental Microbiology.

[56]  C. Cobb Microbes, inflammation, scaling and root planing, and the periodontal condition. , 2008, Journal of dental hygiene : JDH.

[57]  B. Quesnel Dormant tumor cells as a therapeutic target? , 2008, Cancer letters.

[58]  E. Weiss,et al.  Potential Oral Health Benefits of Cranberry , 2008, Critical reviews in food science and nutrition.

[59]  M. Hattori,et al.  Determination of the Genome Sequence of Porphyromonas gingivalis Strain ATCC 33277 and Genomic Comparison with Strain W83 Revealed Extensive Genome Rearrangements in P. gingivalis , 2008, DNA research : an international journal for rapid publication of reports on genes and genomes.

[60]  S. Mazmanian,et al.  A microbial symbiosis factor prevents intestinal inflammatory disease , 2008, Nature.

[61]  I. Weissman,et al.  Stems Cells and the Pathways to Aging and Cancer , 2008, Cell.

[62]  J. Potempa,et al.  Friendly fire against neutrophils: proteolytic enzymes confuse the recognition of apoptotic cells by macrophages. , 2008, Biochimie.

[63]  P. Arlen Novel approaches for the treatment of prostate cancer , 2008 .

[64]  K. Okuda,et al.  Stimulation of Fusobacterium nucleatum biofilm formation by Porphyromonas gingivalis. , 2007, Oral microbiology and immunology.

[65]  C. Andry,et al.  Resolvin E1 Regulates Inflammation at the Cellular and Tissue Level and Restores Tissue Homeostasis In Vivo1 , 2007, The Journal of Immunology.

[66]  G. Seymour,et al.  Relationship between periodontal infections and systemic disease. , 2007, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[67]  R. Barrangou,et al.  CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes , 2007, Science.

[68]  J. Molnár,et al.  Review. Comparison of multidrug resistant efflux pumps of cancer and bacterial cells with respect to the same inhibitory agents. , 2007, In vivo.

[69]  M. Fukuda,et al.  IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs1 , 2007, The Journal of Immunology.

[70]  A. Roberts,et al.  Genetic basis of horizontal gene transfer among oral bacteria. , 2006, Periodontology 2000.

[71]  A. Haffajee,et al.  Identification of oral bacteria associated with crevicular epithelial cells from chronic periodontitis lesions. , 2006, Journal of medical microbiology.

[72]  F. Yoshimura,et al.  Effects of Various Growth Conditions in a Chemostat on Expression of Virulence Factors in Porphyromonas gingivalis , 2006, Applied and Environmental Microbiology.

[73]  J. Rudney,et al.  The vital status of human buccal epithelial cells and the bacteria associated with them. , 2006, Archives of oral biology.

[74]  S. Shizukuishi,et al.  Streptococcus gordonii utilizes several distinct gene functions to recruit Porphyromonas gingivalis into a mixed community , 2006, Molecular microbiology.

[75]  J. A. Aas,et al.  Defining the Normal Bacterial Flora of the Oral Cavity , 2005, Journal of Clinical Microbiology.

[76]  Forest Rohwer,et al.  Here a virus, there a virus, everywhere the same virus? , 2005, Trends in microbiology.

[77]  Kenji Yamamoto,et al.  A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems , 2005, Infection and Immunity.

[78]  P. Taylor,et al.  Isolation of bacteriophages from the oral cavity , 2004, Letters in applied microbiology.

[79]  M. Ajello,et al.  Both lactoferrin and iron influence aggregation and biofilm formation in Streptococcus mutans , 2004, Biometals.

[80]  P. Veith,et al.  Porphyromonas gingivalis gingipains: the molecular teeth of a microbial vampire. , 2003, Current protein & peptide science.

[81]  P. Stewart,et al.  A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance , 2003, Nature.

[82]  Christopher Post,et al.  The application of biofilm science to the study and control of chronic bacterial infections. , 2003, The Journal of clinical investigation.

[83]  Ian T. Paulsen,et al.  Complete Genome Sequence of the Oral Pathogenic Bacterium Porphyromonas gingivalis Strain W83 , 2003, Journal of bacteriology.

[84]  V. Baelum,et al.  Defining and classifying periodontitis: need for a paradigm shift? , 2003, European journal of oral sciences.

[85]  J. Costerton,et al.  Biofilms as complex differentiated communities. , 2002, Annual review of microbiology.

[86]  R. Thornton,et al.  Human gingival fibroblasts produce nitric oxide in response to proinflammatory cytokines. , 2002, Journal of periodontology.

[87]  D. Hinode,et al.  Purification and Characterization of Arginine Carboxypeptidase Produced by Porphyromonas gingivalis , 2002, Infection and Immunity.

[88]  D. Hinode,et al.  Consumption of Peptide-derived Arginine by a Periodontopathogenic Bacterium, Porphyromonas gingivalis , 2001 .

[89]  H. Jenkinson,et al.  Subgingival colonization by Porphyromonas gingivalis. , 2000, Oral microbiology and immunology.

[90]  G. O’Toole,et al.  Microbial Biofilms: from Ecology to Molecular Genetics , 2000, Microbiology and Molecular Biology Reviews.

[91]  S. Socransky,et al.  Microbial composition of supra- and subgingival plaque in subjects with adult periodontitis. , 2000, Journal of clinical periodontology.

[92]  J. Potempa,et al.  Role of bacterial proteinases in matrix destruction and modulation of host responses. , 2000, Periodontology 2000.

[93]  S. Socransky,et al.  Comparison of the microbiota of supra- and subgingival plaque in health and periodontitis. , 2000, Journal of clinical periodontology.

[94]  N. López Occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in progressive adult periodontitis. , 2000, Journal of periodontology.

[95]  J. Potempa,et al.  Purification, Characterization, and Sequence Analysis of a Potential Virulence Factor from Porphyromonas gingivalis, Peptidylarginine Deiminase , 1999, Infection and Immunity.

[96]  H. Kuramitsu Proteases of Porphyromonas gingivalis: what don't they do? , 1998, Oral microbiology and immunology.

[97]  S. Socransky,et al.  Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects. , 1998, Journal of clinical periodontology.

[98]  S. Socransky,et al.  Microbial complexes in subgingival plaque. , 1998, Journal of clinical periodontology.

[99]  K. Yamamoto,et al.  Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease. , 1998, Journal of biochemistry.

[100]  I. Chapple Reactive oxygen species and antioxidants in inflammatory diseases. , 1997, Journal of clinical periodontology.

[101]  A. V. van Winkelhoff,et al.  Temperate bacteriophages are common among Actinobacillus actinomycetemcomitans isolates from periodontal pockets. , 1995, Journal of periodontal research.

[102]  R. Gmür,et al.  Interdental Supragingival Plaque—A Natural Habitat of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Campylobacter rectus, and Prevotella nigrescens , 1994, Journal of dental research.

[103]  S. Socransky,et al.  Microbial etiological agents of destructive periodontal diseases. , 1994, Periodontology 2000.

[104]  W E Moore,et al.  The bacteria of periodontal diseases. , 1994, Periodontology 2000.

[105]  G. Koch,et al.  Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. , 1994, Journal of periodontology.

[106]  S. Calderwood,et al.  Role of iron in regulation of virulence genes , 1993, Clinical Microbiology Reviews.

[107]  J. Potempa,et al.  Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis. , 1992, The Journal of biological chemistry.

[108]  W. Moore,et al.  The microflora of periodontal sites showing active destructive progression. , 1991, Journal of clinical periodontology.

[109]  Julia T. Choi,et al.  Clinical, microbiological and immunological studies on recurrent periodontal disease. , 1990, Journal of clinical periodontology.

[110]  S. Socransky,et al.  The predominant cultivable microbiota of active and inactive lesions of destructive periodontal diseases. , 1988, Journal of clinical periodontology.

[111]  A. J. Laws,et al.  Suspected periodontopathic microorganisms and their oral habitats in young children. , 1987, Oral Microbiology and Immunology.

[112]  H. Dvorak Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. , 1986, The New England journal of medicine.

[113]  R. Page,et al.  Chronic inflammatory gingival and periodontal disease. , 1978, JAMA.

[114]  B. Gottlieb The Formation of the Pocket: Diffuse Atrophy of Alveolar Bone* , 1928 .

[115]  Mya Breitbart,et al.  Marine viruses: truth or dare. , 2012, Annual review of marine science.

[116]  Christine L. Sun,et al.  Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time. , 2011, Genome research.

[117]  C. Fuqua,et al.  Bacterial competition: surviving and thriving in the microbial jungle , 2010, Nature Reviews Microbiology.

[118]  K. Lewis,et al.  Persister cells. , 2010, Annual review of microbiology.

[119]  D. Fine,et al.  Macrophage inflammatory protein-1alpha: a salivary biomarker of bone loss in a longitudinal cohort study of children at risk for aggressive periodontal disease? , 2009, Journal of periodontology.

[120]  J. R. van der Ploeg Analysis of CRISPR in Streptococcus mutans suggests frequent occurrence of acquired immunity against infection by M102-like bacteriophages. , 2009, Microbiology.

[121]  Relationship Between Intake of Green Tea and Periodontal Disease , 2009 .

[122]  John C. Gunsolley,et al.  Macrophage Inflammatory Protein‐1α: A Salivary Biomarker of Bone Loss in a Longitudinal Cohort Study of Children at Risk for Aggressive Periodontal Disease? , 2009 .

[123]  J. Potempa,et al.  A new insight into phagocytosis of apoptotic cells: proteolytic enzymes divert the recognition and clearance of polymorphonuclear leukocytes by macrophages , 2007, Cell Death and Differentiation.

[124]  T. Olczak,et al.  Iron and heme utilization in Porphyromonas gingivalis. , 2005, FEMS microbiology reviews.

[125]  Kelli R. Illyes Nonsurgical periodontal therapy. , 2004, Periodontology 2000.

[126]  S. Socransky,et al.  Implications of periodontal microbiology for the treatment of periodontal infections. , 1994, Compendium (Newtown, Pa.). Supplement.

[127]  Socransky Ss,et al.  Implications of periodontal microbiology for the treatment of periodontal infections. , 1994 .

[128]  N. Lang,et al.  Suspected periodontopathogens in erupting third molar sites of periodontally healthy individuals. , 1990, Journal of clinical periodontology.

[129]  E. Ohara,et al.  Cleavage action of a trypsin-like protease from Bacteroides gingivalis 381 on reduced egg-white lysozyme. , 1989, Archives of oral biology.

[130]  Susan M. Huse,et al.  Defining the healthy " core microbiome " of oral microbial communities , 2017 .