{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:06:37Z","timestamp":1791270397446,"version":"4.1.0"},"reference-count":101,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The microbial community present in the human mouth is engaged in a complex network of diverse metabolic activities. In addition to serving as energy and building-block sources, metabolites are key players in interspecies and host-pathogen interactions. Metabolites are also implicated in triggering the local inflammatory response, which can affect systemic conditions such as atherosclerosis, obesity, and diabetes. While the genome of several oral pathogens has been sequenced, quantitative understanding of the metabolic functions of any oral pathogen at the system level has not been explored yet. Here we pursue the computational construction and analysis of the genome-scale metabolic network of<jats:italic>Porphyromonas gingivalis<\/jats:italic>, a gram-negative anaerobe that is endemic in the human population and largely responsible for adult periodontitis. Integrating information from the genome, online databases, and literature screening, we built a stoichiometric model that encompasses 679 metabolic reactions. By using flux balance approaches and automated network visualization, we analyze the growth capacity under amino-acid-rich medium and provide evidence that amino acid preference and cytotoxic by-product secretion rates are suitably reproduced by the model. To provide further insight into the basic metabolic functions of<jats:italic>P. gingivalis<\/jats:italic>and suggest potential drug targets, we study systematically how the network responds to any reaction knockout. We focus specifically on the lipopolysaccharide biosynthesis pathway and identify eight putative targets, one of which has been recently verified experimentally. The current model, which is amenable to further experimental testing and refinements, could prove useful in evaluating the oral microbiome dynamics and in the development of novel biomedical applications.<\/jats:p>","DOI":"10.1128\/jb.01123-08","type":"journal-article","created":{"date-parts":[[2008,10,18]],"date-time":"2008-10-18T00:59:46Z","timestamp":1224291586000},"page":"74-90","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":68,"title":["Metabolic Network Model of a Human Oral Pathogen"],"prefix":"10.1128","volume":"191","author":[{"given":"Varun","family":"Mazumdar","sequence":"first","affiliation":[{"name":"Program in Bioinformatics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan S.","family":"Snitkin","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salomon","family":"Amar","sequence":"additional","affiliation":[{"name":"School of Dental Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Segre\u0300","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics"},{"name":"Department of Biology and Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/oxfordjournals.jbchem.a021937","volume":"123","year":"1998","unstructured":"Abe, N., T. Kadowaki, K. Okamoto, K. Nakayama, M. Ohishi, and K. Yamamoto. 1998. Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease. J. Biochem. 123 : 305-312.","journal-title":"J. Biochem."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1161\/01.ATV.0000078603.90302.4A","volume":"23","year":"2003","unstructured":"Amar, S., N. Gokce, S. Morgan, M. Loukideli, T. E. Van Dyke, and J. A. Vita. 2003. Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation. Arterioscler. Thromb. Vasc. Biol. 23 : 1245-1249.","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"e_1_3_2_4_2","first-page":"RA291","volume":"9","year":"2003","unstructured":"Amar, S., and X. Han. 2003. The impact of periodontal infection on systemic diseases. Med. Sci. Monit. 9 : RA291-RA299.","journal-title":"Med. Sci. Monit."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"20466","DOI":"10.1073\/pnas.0710335105","volume":"104","year":"2007","unstructured":"Amar, S., Q. Zhou, Y. Shaik-Dasthagirisaheb, and S. Leeman. 2007. Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge. Proc. Natl. Acad. Sci. USA 104 : 20466-20471.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1574-6968.2002.tb11024.x","volume":"207","year":"2002","unstructured":"Arimoto, T., T. Ansai, W. Yu, A. J. Turner, and T. Takehara. 2002. Kinetic analysis of PPi-dependent phosphofructokinase from Porphyromonas gingivalis. FEMS Microbiol. Lett. 207 : 35-38.","journal-title":"FEMS Microbiol. Lett."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4049\/jimmunol.160.1.403","volume":"160","year":"1998","unstructured":"Assuma, R., T. Oates, D. Cochran, S. Amar, and D. T. Graves. 1998. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J. Immunol. 160 : 403-409.","journal-title":"J. Immunol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nprot.2007.99","volume":"2","year":"2007","unstructured":"Becker, S. A., A. M. Feist, M. L. Mo, G. Hannum, B. O. Palsson, and M. J. Herrgard. 2007. Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox. Nat. Protoc. 2 : 727-738.","journal-title":"Nat. Protoc."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2180-5-8","volume":"5","year":"2005","unstructured":"Becker, S. A., and B. O. Palsson. 2005. Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. BMC Microbiol. 5 : 8.","journal-title":"BMC Microbiol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000057864","volume":"36","year":"2002","unstructured":"Bradshaw, D. J., P. D. Marsh, R. J. Hodgson, and J. M. Visser. 2002. Effects of glucose and fluoride on competition and metabolism within in vitro dental bacterial communities and biofilms. Caries Res. 36 : 81-86.","journal-title":"Caries Res."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1902\/jop.2007.060436","volume":"78","year":"2007","unstructured":"Brennan, R. M., R. J. Genco, G. E. Wilding, K. M. Hovey, M. Trevisan, and J. Wactawski-Wende. 2007. Bacterial species in subgingival plaque and oral bone loss in postmenopausal women. J. Periodontol. 78 : 1051-1061.","journal-title":"J. Periodontol."},{"key":"e_1_3_2_12_2","first-page":"635","volume":"43","year":"2007","unstructured":"Briukhanov, A. L., and A. I. Netrusov. 2007. Aerotolerance of strictly anaerobic microorganisms and factors of defense against oxidative stress: a review. Prikl. Biokhim. Mikrobiol. 43 : 635-652. (In Russian.)","journal-title":"Prikl. Biokhim. Mikrobiol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nature05685","volume":"446","year":"2007","unstructured":"Chait, R., A. Craney, and R. Kishony. 2007. Antibiotic interactions that select against resistance. Nature 446 : 668-671.","journal-title":"Nature"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.4231-4236.1999"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5367-5378.2005"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"e176","DOI":"10.1371\/journal.pbio.0030176","volume":"3","year":"2005","unstructured":"Cirz, R. T., J. K. Chin, D. R. Andes, V. de Crecy-Lagard, W. A. Craig, and F. E. Romesberg. 2005. Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol. 3 : e176.","journal-title":"PLoS Biol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.5041-5051.2004"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1574-6968.2006.00221.x","volume":"258","year":"2006","unstructured":"Diaz-Torres, M. L., A. Villedieu, N. Hunt, R. McNab, D. A. Spratt, E. Allan, P. Mullany, and M. Wilson. 2006. Determining the antibiotic resistance potential of the indigenous oral microbiota of humans using a metagenomic approach. FEMS Microbiol. Lett. 258 : 257-262.","journal-title":"FEMS Microbiol. Lett."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1177\/154411130301400303","volume":"14","year":"2003","unstructured":"Duncan, M. J. 2003. Genomics of oral bacteria. Crit. Rev. Oral Biol. Med. 14 : 175-187.","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1046\/j.1462-2920.2002.00282.x","volume":"4","year":"2002","unstructured":"Edwards, J. S., M. Covert, and B. Palsson. 2002. Metabolic modeling of microbes: the flux-balance approach. Environ. Microbiol. 4 : 133-140.","journal-title":"Environ. Microbiol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1073\/pnas.97.10.5528","volume":"97","year":"2000","unstructured":"Edwards, J. S., and B. O. Palsson. 2000. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc. Natl. Acad. Sci. USA 97 : 5528-5533.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-1-1","volume":"1","year":"2000","unstructured":"Edwards, J. S., and B. O. Palsson. 2000. Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions. BMC Bioinform. 1 : 1.","journal-title":"BMC Bioinform."},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"13134","DOI":"10.1073\/pnas.2235812100","volume":"100","year":"2003","unstructured":"Famili, I., J. Forster, J. Nielsen, and B. O. Palsson. 2003. Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network. Proc. Natl. Acad. Sci. USA 100 : 13134-13139.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/msb4100155","volume":"3","year":"2007","unstructured":"Feist, A. M., C. S. Henry, J. L. Reed, M. Krummenacker, A. R. Joyce, P. D. Karp, L. J. Broadbelt, V. Hatzimanikatis, and B. O. Palsson. 2007. A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1,260 ORFs and thermodynamic information. Mol. Systems Biol. 3 : 121.","journal-title":"Mol. Systems Biol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nbt1401","volume":"26","year":"2008","unstructured":"Feist, A. M., and B. O. Palsson. 2008. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat. Biotechnol. 26 : 659-667.","journal-title":"Nat. Biotechnol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1101\/gr.234503","volume":"13","year":"2003","unstructured":"Forster, J., I. Famili, P. Fu, B. O. Palsson, and J. Nielsen. 2003. Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res. 13 : 244-253.","journal-title":"Genome Res."},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1471-2105-5-76","volume":"5","year":"2004","unstructured":"Green, M. L., and P. D. Karp. 2004. A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases. BMC Bioinform. 5 : 76.","journal-title":"BMC Bioinform."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.91.1.27-32.1966"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1371\/journal.pcbi.0020072","volume":"2","year":"2006","unstructured":"Herrg\u00e5rd, M. J., S. S. Fong, and B. O. Palsson. 2006. Identification of genome-scale metabolic network models using experimentally measured flux profiles. PLoS Comput. Biol. 2 : e72.","journal-title":"PLoS Comput. Biol."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1358\/dot.2006.42.10.1003543","volume":"42","year":"2006","unstructured":"Hoge, M., and S. Amar. 2006. Role of interleukin-1 in bacterial atherogenesis. Drugs Today 42 : 683-688.","journal-title":"Drugs Today"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.3336774","volume":"239","year":"1988","unstructured":"Holt, S. C., J. Ebersole, J. Felton, M. Brunsvold, and K. S. Kornman. 1988. Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. Science 239 : 55-57.","journal-title":"Science"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.biosystems.2005.04.008","volume":"83","year":"2006","unstructured":"Holzh\u00fctter, H.-G. 2006. The generalized flux-minimization method and its application to metabolic networks affected by enzyme deficiencies. Biosystems 83 : 98-107.","journal-title":"Biosystems"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1111\/j.1432-1033.2004.04213.x","volume":"271","year":"2004","unstructured":"Holzh\u00fctter, H.-G. 2004. The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks. Eur. J. Biochem. 271 : 2905-2922.","journal-title":"Eur. J. Biochem."},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"W625","DOI":"10.1093\/nar\/gkm295","volume":"35","year":"2007","unstructured":"Hu, Z., D. M. Ng, T. Yamada, C. Chen, S. Kawashima, J. Mellor, B. Linghu, M. Kanehisa, J. M. Stuart, and C. DeLisi. 2007. VisANT 3.0: new modules for pathway visualization, editing, prediction and construction. Nucleic Acids Res. 35 : W625-W632.","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature01149","volume":"420","year":"2002","unstructured":"Ibarra, R. U., J. S. Edwards, and B. O. Palsson. 2002. Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth. Nature 420 : 186-189.","journal-title":"Nature"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1093\/bioinformatics\/bti245","volume":"21","year":"2005","unstructured":"Imieli\u0144ski, M., C. Belta, A. Halasz, and H. Rubin. 2005. Investigating metabolite essentiality through genome-scale analysis of Escherichia coli production capabilities. Bioinformatics 21 : 2008-2016.","journal-title":"Bioinformatics"},{"key":"e_1_3_2_37_2","first-page":"223","volume":"44","year":"1908","unstructured":"Jaccard, P. 1908. Nouvelles recherches sur la distribution florale. Bull. Soc. Vaudoise Sci. Nat. 44 : 223-270.","journal-title":"Bull. Soc. Vaudoise Sci. Nat."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1752-0509-1-26","volume":"1","year":"2007","unstructured":"Jamshidi, N., and B. O. Palsson. 2007. Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets. BMC Systems Biol. 1 : 26.","journal-title":"BMC Systems Biol."},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.copbio.2003.08.001","volume":"14","year":"2003","unstructured":"Kauffman, K. J., P. Prakash, and J. S. Edwards. 2003. Advances in flux balance analysis. Curr. Opin. Biotechnol. 14 : 491-496.","journal-title":"Curr. Opin. Biotechnol."},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s10266-006-0060-6","volume":"94","year":"2006","unstructured":"Kim, J., and S. Amar. 2006. Periodontal disease and systemic conditions: a bidirectional relationship. Odontology 94 : 10-21.","journal-title":"Odontology"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.8.2098-2106.1995"},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1574-6968.1993.tb06076.x","volume":"108","year":"1993","unstructured":"Kumada, H., S. Kondo, T. Umemoto, and K. Hisatsune. 1993. Chemical structure of the 2-keto-3-deoxyoctonate region of lipopolysaccharide isolated from Porphyromonas (Bacteroides) gingivalis. FEMS Microbiol. Lett. 108 : 75-79.","journal-title":"FEMS Microbiol. Lett."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00024-07"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.4.1244-1263.1998"},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1902\/annals.2001.6.1.146","volume":"6","year":"2001","unstructured":"Lamster, I. B., and E. Lalla. 2001. Periodontal disease and diabetes mellitus: discussion, conclusions, and recommendations. Ann. Periodontol. 6 : 146-149.","journal-title":"Ann. Periodontol."},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1902\/jop.2007.060368","volume":"78","year":"2007","unstructured":"Leon, R., N. Silva, A. Ovalle, A. Chaparro, A. Ahumada, M. Gajardo, M. Martinez, and J. Gamonal. 2007. Detection of Porphyromonas gingivalis in the amniotic fluid in pregnant women with a diagnosis of threatened premature labor. J. Periodontol. 78 : 1249-1255.","journal-title":"J. Periodontol."},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.cell.2006.02.017","volume":"124","year":"2006","unstructured":"Ley, R. E., D. A. Peterson, and J. I. Gordon. 2006. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124 : 837-848.","journal-title":"Cell"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.7.3915-3922.2002"},{"key":"e_1_3_2_49_2","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1161\/hc0702.104178","volume":"105","year":"2002","unstructured":"Li, L., E. Messas, E. L. Batista, Jr., R. A. Levine, and S. Amar. 2002. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation 105 : 861-867.","journal-title":"Circulation"},{"key":"e_1_3_2_50_2","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1210\/en.2004-0737","volume":"145","year":"2004","unstructured":"Lu, H., M. Raptis, E. Black, M. Stan, S. Amar, and D. T. Graves. 2004. Influence of diabetes on the exacerbation of an inflammatory response in cardiovascular tissue. Endocrinology 145 : 4934-4939.","journal-title":"Endocrinology"},{"key":"e_1_3_2_51_2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.atherosclerosis.2007.02.023","volume":"197","year":"2008","unstructured":"Madan, M., B. Bishayi, M. Hoge, and S. Amar. 2008. Atheroprotective role of interleukin-6 in diet- and\/or pathogen-associated atherosclerosis using an ApoE heterozygote murine model. Atherosclerosis 197 : 504-514.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_52_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ymben.2003.09.002","volume":"5","year":"2003","unstructured":"Mahadevan, R., and C. H. Schilling. 2003. The effects of alternate optimal solutions in constraint-based genome-scale metabolic models. Metab. Eng. 5 : 264-276.","journal-title":"Metab. Eng."},{"key":"e_1_3_2_53_2","unstructured":"GNU linear programming kit 2001"},{"key":"e_1_3_2_54_2","doi-asserted-by":"crossref","first-page":"11889","DOI":"10.1073\/pnas.0704662104","volume":"104","year":"2007","unstructured":"Marcy, Y., C. Ouverney, E. M. Bik, T. L\u00f6sekann, N. Ivanova, H. G. Martin, E. Szeto, D. Platt, P. Hugenholtz, D. A. Relman, and S. R. Quake. 2007. Dissecting biological \u201cdark matter\u201d with single-cell genetic analysis of rare and uncultivated TM7 microbes from the human mouth. Proc. Natl. Acad. Sci. USA 104 : 11889-11894.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.1.274-284.2003"},{"key":"e_1_3_2_56_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1369-5274(98)80147-1","volume":"1","year":"1998","unstructured":"Meyer, D. H., and P. M. Fives-Taylor. 1998. Oral pathogens: from dental plaque to cardiac disease. Curr. Opin. Microbiol. 1 : 88-95.","journal-title":"Curr. Opin. Microbiol."},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","first-page":"W182","DOI":"10.1093\/nar\/gkm321","volume":"35","year":"2007","unstructured":"Moriya, Y., M. Itoh, S. Okuda, A. C. Yoshizawa, and M. Kanehisa. 2007. KAAS: an automatic genome annotation and pathway reconstruction server. Nucleic Acids Res. 35 : W182-W185.","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_2_58_2","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1099\/jmm.0.47289-0","volume":"56","year":"2007","unstructured":"Nagano, K., Y. Murakami, K. Nishikawa, J. Sakakibara, K. Shimozato, and F. Yoshimura. 2007. Characterization of RagA and RagB in Porphyromonas gingivalis: study using gene-deletion mutants. J. Med. Microbiol. 56 : 1536-1548.","journal-title":"J. Med. Microbiol."},{"key":"e_1_3_2_59_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.atherosclerosis.2007.01.039","volume":"196","year":"2008","unstructured":"Nakamura, N., M. Yoshida, M. Umeda, Y. Huang, S. Kitajima, Y. Inoue, I. Ishikawa, and T. Iwai. 2008. Extended exposure of lipopolysaccharide fraction from Porphyromonas gingivalis facilitates mononuclear cell adhesion to vascular endothelium via Toll-like receptor-2-dependent mechanism. Atherosclerosis 196 : 59-67.","journal-title":"Atherosclerosis"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00261-06"},{"key":"e_1_3_2_61_2","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1016\/S0021-9258(18)94337-1","volume":"244","year":"1969","unstructured":"Namba, Y., K. Yoshizawa, A. Ejima, T. Hayashi, and T. Kaneda. 1969. Coenzyme A- and nicotinamide adenine dinucleotide-dependent branched chain agr-keto acid dehydrogenase. I. Purification and properties of the enzyme from Bacillus subtilis. J. Biol. Chem. 244 : 4437-4447.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.18.5591-5601.2003"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1752-0509-2-79","volume":"2","year":"2008","unstructured":"Nogales, J., B. Palsson, and I. Thiele. 2008. A genome-scale metabolic reconstruction of Pseudomonas putida KT2440: iJN746 as a cell factory. BMC Systems Biol. 2 : 79.","journal-title":"BMC Systems Biol."},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01583-07"},{"key":"e_1_3_2_65_2","doi-asserted-by":"crossref","first-page":"28791","DOI":"10.1074\/jbc.M703759200","volume":"282","year":"2007","unstructured":"Oh, Y.-K., B. O. Palsson, S. M. Park, C. H. Schilling, and R. Mahadevan. 2007. Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J. Biol. Chem. 282 : 28791-28799.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_66_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.femsre.2004.09.001","volume":"29","year":"2005","unstructured":"Olczak, T., W. Simpson, X. Liu, and C. A. Genco. 2005. Iron and heme utilization in Porphyromonas gingivalis. FEMS Microbiol. Rev. 29 : 119-144.","journal-title":"FEMS Microbiol. Rev."},{"key":"e_1_3_2_67_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1471-2180-5-39","volume":"5","year":"2005","unstructured":"Oliveira, A. P., J. Nielsen, and J. F\u00f6rster. 2005. Modeling Lactococcus lactis using a genome-scale flux model. BMC Microbiol. 5 : 39.","journal-title":"BMC Microbiol."},{"key":"e_1_3_2_68_2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0968-0004(03)00064-1","volume":"28","year":"2003","unstructured":"Papin, J. A., N. D. Price, S. J. Wiback, D. A. Fell, and B. O. Palsson. 2003. Metabolic pathways in the post-genome era. Trends Biochem. Sci. 28 : 250-258.","journal-title":"Trends Biochem. Sci."},{"key":"e_1_3_2_69_2","first-page":"1887","volume":"3","year":"2007","unstructured":"Resendis-Antonio, O., J. L. Reed, S. Encarnaci\u00f3n, J. Collado-Vides, and B. O. Palsson. 2007. Metabolic reconstruction and modeling of nitrogen fixation in Rhizobium etli. PLoS Comput. Biol. 3 : 1887-1895.","journal-title":"PLoS Comput. Biol."},{"key":"e_1_3_2_70_2","first-page":"1","year":"1988","unstructured":"Rietschel, E. T., L. Brade, U. Schade, U. Seydel, U. Z\u00e4ringer, S. Kusumoto, and H. Brade. 1988. Bacterial endotoxins: properties and structure of biologically active domains, p. 1-41. In E. Schrinner, M. H. Richmond, G. Seibert, and U. Schwarz (ed.), Surface structures of microorganisms and their interactions with the mammalian host. VCH Verlagsgesellschaft GmbH, Weinheim, Federal Republic of Germany.","journal-title":"Surface structures of microorganisms and their interactions with the mammalian host."},{"key":"e_1_3_2_71_2","first-page":"187","volume":"1","year":"1984","unstructured":"Rietschel, E. T., H.-W. Wollenweber, H. Brade, U. Z\u00e4ringer, B. Lindner, U. Seydel, H. Bradaczek, G. Barnickel, H. Labischinski, and P. Giesbrecht. 1984. Structure and conformation of the lipid A component of lipopolysaccharides, p. 187-220. In E. T. Rietschel (ed.), Handbook of endotoxin, vol. 1. Elsevier Science Publishing B.V., Amsterdam, The Netherlands.","journal-title":"Handbook of endotoxin"},{"key":"e_1_3_2_72_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10753-004-6641-z","volume":"28","year":"2004","unstructured":"Rosenstein, E. D., R. A. Greenwald, L. J. Kushner, and G. Weissmann. 2004. Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation 28 : 311-318.","journal-title":"Inflammation"},{"key":"e_1_3_2_73_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1574-6968.2007.00736.x","volume":"272","year":"2007","unstructured":"Roth, G. A., H. J. Ankersmit, V. B. Brown, P. N. Papapanou, A. M. Schmidt, and E. Lalla. 2007. Porphyromonas gingivalis infection and cell death in human aortic endothelial cells. FEMS Microbiol. Lett. 272 : 106-113.","journal-title":"FEMS Microbiol. Lett."},{"key":"e_1_3_2_74_2","first-page":"406","volume":"4","year":"1987","unstructured":"Saitou, N., and M. Nei. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4 : 406-425.","journal-title":"Mol. Biol. Evol."},{"key":"e_1_3_2_75_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/1471-2105-8-212","volume":"8","year":"2007","unstructured":"Satish Kumar, V., M. S. Dasika, and C. D. Maranas. 2007. Optimization based automated curation of metabolic reconstructions. BMC Bioinform. 8 : 212.","journal-title":"BMC Bioinform."},{"key":"e_1_3_2_76_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/msb4100109","volume":"2","year":"2006","unstructured":"Sauer, U. 2006. Metabolic networks in motion: 13C-based flux analysis. Mol. Systems Biol. 2 : 62.","journal-title":"Mol. Systems Biol."},{"key":"e_1_3_2_77_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/1097-0290(2000)71:4<286::AID-BIT1018>3.0.CO;2-R","volume":"71","year":"2000","unstructured":"Schilling, C. H., J. S. Edwards, D. Letscher, and B. O. Palsson. 2000. Combining pathway analysis with flux balance analysis for the comprehensive study of metabolic systems. Biotechnol. Bioeng. 71 : 286-306.","journal-title":"Biotechnol. Bioeng."},{"key":"e_1_3_2_78_2","unstructured":"Networks in the cell 2008"},{"key":"e_1_3_2_79_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/ng1489","volume":"37","year":"2005","unstructured":"Segr\u00e8, D., A. Deluna, G. M. Church, and R. Kishony. 2005. Modular epistasis in yeast metabolism. Nat. Genet. 37 : 77-83.","journal-title":"Nat. Genet."},{"key":"e_1_3_2_80_2","doi-asserted-by":"crossref","first-page":"15112","DOI":"10.1073\/pnas.232349399","volume":"99","year":"2002","unstructured":"Segr\u00e8, D., D. Vitkup, and G. M. Church. 2002. Analysis of optimality in natural and perturbed metabolic networks. Proc. Natl. Acad. Sci. USA 99 : 15112-15117.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_81_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1089\/153623103322452413","volume":"7","year":"2003","unstructured":"Segr\u00e8, D., J. Zucker, J. Katz, X. Lin, P. D'Haeseleer, W. P. Rindone, P. Kharchenko, D. H. Nguyen, M. A. Wright, and G. M. Church. 2003. From annotated genomes to metabolic flux models and kinetic parameter fitting. OMICS 7 : 301-316.","journal-title":"OMICS"},{"key":"e_1_3_2_82_2","first-page":"1026","volume":"101","year":"2008","unstructured":"Senger, R. S., and E. T. Papoutsakis. 2008. Genome-scale model for Clostridium acetobutylicum. I. Metabolic network resolution and analysis. Biotechnol. Bioeng. 101 : 1026-1052.","journal-title":"Biotechnol. Bioeng."},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01798.x"},{"key":"e_1_3_2_84_2","first-page":"86","year":"1993","unstructured":"Shah, H. N., and S. E. Gharbia. 1993. Batch culture and physiological properties, p. 86-102. In D. M. Haroun, N. Shah, and R. J. Genco (ed.), Biology of the species Porphyromonas gingivalis. CRC Press, Inc., Boca Raton, FL.","journal-title":"Biology of the species Porphyromonas gingivalis."},{"key":"e_1_3_2_85_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1399-302X.1989.tb00401.x","volume":"4","year":"1989","unstructured":"Shah, H. N., S. V. Seddon, and S. E. Gharbia. 1989. Studies on the virulence properties and metabolism of pleiotropic mutants of Porphyromonas gingivalis (Bacteroides gingivalis) W50. Oral Microbiol. Immunol. 4 : 19-23.","journal-title":"Oral Microbiol. Immunol."},{"key":"e_1_3_2_86_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/BF01577587","volume":"15","year":"1987","unstructured":"Shah, H. N., and R. A. D. Williams. 1987. Catabolism of aspartate and asparagine by Bacteroides intermedius and Bacteroides gingivalis. Curr. Microbiol. 15 : 313-318.","journal-title":"Curr. Microbiol."},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.6.2736-2742.1998"},{"key":"e_1_3_2_88_2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/j.1875-595X.2001.tb00854.x","volume":"51","year":"2001","unstructured":"Slots, J., and J. J. Kamma. 2001. General health risk of periodontal disease. Int. Dent. J. 51 : 417-427.","journal-title":"Int. Dent. J."},{"key":"e_1_3_2_89_2","doi-asserted-by":"crossref","first-page":"R140","DOI":"10.1186\/gb-2008-9-9-r140","volume":"9","year":"2008","unstructured":"Snitkin, E. S., A. M. Dudley, D. M. Janse, K. Wong, G. M. Church, and D. Segr\u00e8. 2008. Model-driven analysis of experimentally determined growth phenotypes for 465 deletion mutants under 16 different conditions. Genome Biol. 9 : R140.","journal-title":"Genome Biol."},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.88.1.200-209.1964"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.17.4704-4710.2000"},{"key":"e_1_3_2_92_2","doi-asserted-by":"crossref","first-page":"13777","DOI":"10.1073\/pnas.0605988103","volume":"103","year":"2006","unstructured":"Tang, X., D. Metzger, S. Leeman, and S. Amar. 2006. LPS-induced TNF-alpha factor (LITAF)-deficient mice express reduced LPS-induced cytokine: evidence for LITAF-dependent LPS signaling pathways. Proc. Natl. Acad. Sci. USA 103 : 13777-13782.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.16.5818-5830.2005"},{"key":"e_1_3_2_94_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1600-0765.1997.tb01392.x","volume":"32","year":"1997","unstructured":"Travis, J., R. Pike, T. Imamura, and J. Potempa. 1997. Porphyromonas gingivalis proteinases as virulence factors in the development of periodontitis. J. Periodontal Res. 32 : 120-125.","journal-title":"J. Periodontal Res."},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06244"},{"key":"e_1_3_2_96_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1099\/jmm.0.47679-0","volume":"57","year":"2008","unstructured":"Uehara, A., M. Naito, T. Imamura, J. Potempa, J. Travis, K. Nakayama, and H. Takada. 2008. Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis. J. Med. Microbiol. 57 : 500-507.","journal-title":"J. Med. Microbiol."},{"key":"e_1_3_2_97_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1006\/jtbi.1993.1203","volume":"165","year":"1993","unstructured":"Varma, A., and B. O. Palsson. 1993. Metabolic capabilities of Escherichia coli. II. Optimal growth patterns. J. Theor. Biol. 165 : 503-522.","journal-title":"J. Theor. Biol."},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00008-07"},{"key":"e_1_3_2_99_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1056\/NEJM199002083220606","volume":"322","year":"1990","unstructured":"Williams, R. C. 1990. Periodontal disease. N. Engl. J. Med. 322 : 373-382.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_100_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1034\/j.1600-0765.2001.00608.x","volume":"36","year":"2001","unstructured":"Xiao, Y., C. L. Bunn, and P. M. Bartold. 2001. Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts. J. Periodontal Res. 36 : 25-31.","journal-title":"J. Periodontal Res."},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.12.6912-6916.2000"},{"key":"e_1_3_2_102_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00284-002-3916-1","volume":"47","year":"2003","unstructured":"Yoshioka, M., D. Grenier, and D. Mayrand. 2003. Monitoring the uptake of protein-derived peptides by Porphyromonas gingivalis with fluorophore-labeled substrates. Curr. Microbiol. 47 : 1-4.","journal-title":"Curr. Microbiol."}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.01123-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.01123-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T16:14:51Z","timestamp":1684599291000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.01123-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":101,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,1]]}},"alternative-id":["10.1128\/JB.01123-08"],"URL":"https:\/\/doi.org\/10.1128\/jb.01123-08","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1]]},"assertion":[{"value":"2008-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}