{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:57:18Z","timestamp":1790488638853,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ6\/00292"],"award-info":[{"award-number":["2019\/33\/B\/NZ6\/00292"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human oral and gut microbiomes are crucial for maintenance of homeostasis in the human body. Porphyromonas gingivalis, the key etiologic agent of chronic periodontitis, can cause dysbiosis in the mouth and gut, which results in local and systemic infectious inflammatory diseases. Our previous work resulted in extensive biochemical and functional characterization of one of the major P. gingivalis heme acquisition systems (Hmu), with the leading role played by the HmuY hemophore-like protein. We continued our studies on the homologous heme acquisition protein (Bvu) expressed by Bacteroides vulgatus, the dominant species of the gut microbiome. Results from spectrophotometric experiments showed that Bvu binds heme preferentially under reducing conditions using Met145 and Met172 as heme iron-coordinating ligands. Bvu captures heme bound to human serum albumin and only under reducing conditions. Importantly, HmuY is able to sequester heme complexed to Bvu. This is the first study demonstrating that B. vulgatus expresses a heme-binding hemophore-like protein, thus increasing the number of members of a novel HmuY-like family. Data gained in this study confirm the importance of HmuY in the context of P. gingivalis survival in regard to its ability to cause dysbiosis also in the gut microbiome.<\/jats:p>","DOI":"10.3390\/ijms22052237","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T20:53:21Z","timestamp":1614200001000},"page":"2237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Porphyromonas gingivalis HmuY and Bacteroides vulgatus Bvu\u2014A Novel Competitive Heme Acquisition Strategy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-4424","authenticated-orcid":false,"given":"Klaudia","family":"Siemi\u0144ska","sequence":"first","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw, 14A F. Joliot-Curie St., 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5067-4244","authenticated-orcid":false,"given":"Patryk","family":"Cierpisz","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw, 14A F. Joliot-Curie St., 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"\u015amiga","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw, 14A F. Joliot-Curie St., 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-8144","authenticated-orcid":false,"given":"Teresa","family":"Olczak","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw, 14A F. Joliot-Curie St., 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1128\/CMR.00008-07","article-title":"Bacteroides: The Good, the Bad, and the Nitty-Gritty","volume":"20","author":"Wexler","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R42","DOI":"10.1186\/gb-2012-13-6-r42","article-title":"Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples","volume":"13","author":"Segata","year":"2012","journal-title":"Genome Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nm.4517","article-title":"Current understanding of the human micro-biome","volume":"24","author":"Gilbert","year":"2018","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S0016-5085(03)00672-3","article-title":"Bacteroides vulgatus protects against Escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice","volume":"125","author":"Waidmann","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1161\/CIRCULATIONAHA.118.033714","article-title":"Bacteoides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis","volume":"138","author":"Yoshida","year":"2018","journal-title":"Circulation"},{"key":"ref_6","first-page":"45","article-title":"The pathogenic role of Bacteroides vulgatus in patients with ulcerative colitis","volume":"30","author":"Bamba","year":"1995","journal-title":"J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-6968.2012.02579.x","article-title":"Porphyromonas gingivalis: An invasive and evasive opportunistic oral pathogen","volume":"333","author":"Bostanci","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrmicro2873","article-title":"The keystone-pathogen hypothesis","volume":"10","author":"Hajishengallis","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1177\/0022034512453589","article-title":"Porphyromonas gingivalis as a potential community activist for disease","volume":"91","author":"Darveau","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"927","DOI":"10.4239\/wjd.v6.i7.927","article-title":"Relationship between diabetes and periodontal infection","volume":"6","author":"Llambes","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nri3785","article-title":"Periodontitis: From microbial immune subversion to systemic inflammation","volume":"15","author":"Hajishengallis","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1586422","DOI":"10.1080\/20002297.2019.1586422","article-title":"Can oral bacteria affect the microbiome of the gut?","volume":"11","author":"Olsen","year":"2019","journal-title":"J. Oral Microbiol."},{"key":"ref_14","first-page":"1","article-title":"Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota","volume":"4","author":"Arimatsu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-07196-7","article-title":"Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis though modulation of the gut microbiota and gut immune system","volume":"7","author":"Sato","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","first-page":"1","article-title":"Talk to your gut: The oral-gut microbiome axis and its immunomodulatory role in the etiology of rheumatoid arthritis","volume":"43","author":"Gabarrini","year":"2018","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cell.2014.09.008","article-title":"Bacteria from Diverse Habitats Colonize and Compete in the Mouse Gut","volume":"159","author":"Seedorf","year":"2014","journal-title":"Cell"},{"key":"ref_18","first-page":"e669","article-title":"Bacteroides fragilis requires the ferrous-iron transporter FeoAB and the CobN-like proteins BtuS1 and BtuS2 for assimilation of iron released from heme","volume":"8","author":"Rocha","year":"2018","journal-title":"Microbiol. Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/omi.12149","article-title":"Haem acquisition mechanisms of Porphyromonas gingivalis-strategies used in polymicrobial community in a haem-limited host environment","volume":"32","author":"Smalley","year":"2017","journal-title":"Mol. Oral Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.bbrc.2015.10.070","article-title":"HmuY is an important virulence factor for Porphyromonas gingivalis growth in the heme-limited host environment and infection of macrophages","volume":"467","author":"Olczak","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1440-1746.1989.tb00858.x","article-title":"Haem in the gut. I. Fate of haemoproteins and the absorption of haem","volume":"4","author":"Young","year":"1989","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1440-1746.1990.tb01824.x","article-title":"Haem in the gut. Part II. Faecal excretion of haem and haem-derived porphyrins and their detection","volume":"5","author":"Young","year":"1990","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"BSR20181325","DOI":"10.1042\/BSR20181325","article-title":"Tannerella forsythia Tfo belongs to Porphyromonas gingivalis HmuY-like family of proteins but differs in heme-binding properties","volume":"38","author":"Bielecki","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1042\/BCJ20190607","article-title":"Prevotella intermedia produces two proteins homologous to Porphyromonas gingivalis HmuY but with different heme coordination mode","volume":"477","author":"Bielecki","year":"2020","journal-title":"Biochem. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"\u015al\u0119zak, P., \u015amiga, M., Smalley, J.W., Siemi\u0144ska, K., and Olczak, T. (2020). Porphyromonas gingivalis HmuY and Streptococcus gordonii GAPDH\u2014Novel Heme Acquisition Strategy in the Oral Microbiome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114150"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1002\/j.1460-2075.1992.tb05535.x","article-title":"Hemin uptake system of Yersinia enterocolitica: Similarities with TonB-dependent systems in gram-negative bacteria","volume":"11","author":"Stojiljkovic","year":"1992","journal-title":"EMBO J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/978-94-007-5561-1_9","article-title":"Heme Uptake and Metabolism in Bacteria","volume":"Volume 12","author":"Benson","year":"2012","journal-title":"Metallomics and the Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00203-007-0309-7","article-title":"Porphyromonas gingivalis HmuY and HmuR: Further characterization of a novel mechanism of heme utilization","volume":"189","author":"Olczak","year":"2007","journal-title":"Arch. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2180-10-134","article-title":"Species specificity, surface exposure, protein expression, immunogenicity, and participation in biofilm formation of Porphyromonas gingivalis HmuY","volume":"10","author":"Olczak","year":"2010","journal-title":"BMC Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.3389\/fmicb.2020.596459","article-title":"Heme competition triggers and increase in the pathogenic potential of Por-phyromonas gingivalis in Porphyromonas gingivalis-Candida albicans mixed biofilm","volume":"11","author":"Guo","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fmicb.2018.00124","article-title":"Worlds Apart\u2014Transcriptome Profiles of Key Oral Microbes in the Periodontal Pocket Compared to Single Laboratory Culture Reflect Synergistic Interactions","volume":"9","author":"Deng","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/npjbiofilms.2015.17","article-title":"Functional biomarkers for chronic periodontitis and insights into the roles of Prevotella nigrescens and Fusobacterium nucleatum; a metatranscriptome analysis","volume":"1","author":"Szafranski","year":"2015","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"W\u00f3jtowicz, H., Guevara, T., Tallant, C., Olczak, M., Sroka, A., Potempa, J., Sola, M., Olczak, T., and Gomis-R\u00fcth, F.X. (2009). Unique Structure and Stability of HmuY, a Novel Heme-Binding Protein of Porphyromonas gingivalis. PLOS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000419"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbrc.2009.03.148","article-title":"Heme environment of Porphyromonas gingivalis HmuY heme-binding protein","volume":"382","author":"Wojtowicz","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Smalley, J.W., Byrne, D.P., Birss, A.J., Wojtowicz, H., Sroka, A., Potempa, J., and Olczak, T. (2011). HmuY haemophore and gingipain proteases constitute a unique syntrophic system of haem acquisition by Porphyromonas gingivalis. PLoS ONE, 6.","DOI":"10.1371\/annotation\/8658727f-cc10-47ba-9c7e-8726f1f94b91"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/omi.12018","article-title":"Evidence of mutualism between two periodontal pathogens: Co-operative haem acquisition by the HmuY haemophore of Porphyromonas gingivalis and the cysteine protease interpain A (InpA) of Prevotella intermedia","volume":"28","author":"Byrne","year":"2013","journal-title":"Mol. Oral Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Benedyk, M., Byrne, D.P., Glowczyk, I., Potempa, J., Olczak, M., Olczak, T., and Smalley, J.W. (2015). Pyocyanin: A contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lung. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118319"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pinsky, M., Roy, U., Moshe, S., Weissman, Z., and Kornitzer, D. (2020). Human Serum Albumin Facilitates Heme-Iron Utilization by Fungi. mBio, 11.","DOI":"10.1128\/mBio.00607-20"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00775-011-0837-0","article-title":"Evidence for pH-dependent multiple conformes in iron(II) heme-human serum albumin: Spectroscopic and kinetic investigation of carbon monoxide binding","volume":"17","author":"Cao","year":"2012","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bocedi, A., De Sanctis, G., Ciaccio, C., Tundo, G.R., Di Masi, A., Fanali, G., Nicoletti, F.P., Fasano, M., Smulevich, G., and Ascenzi, P. (2013). Reciprocal allosteric modulation of carbon monooxide and warfarin binding to ferrous human serum heme-albumin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058842"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0014-5793(91)80292-B","article-title":"The reactivity of cytochrome c with soft ligands","volume":"280","author":"Schejter","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"194107","DOI":"10.1063\/1.2196882","article-title":"Elucidating the hard\/soft acid\/base principle: A perspective based on half-reactions","volume":"124","author":"Ayers","year":"2006","journal-title":"J. Chem. Phys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.freeradbiomed.2012.10.554","article-title":"Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota","volume":"55","author":"Espey","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1053\/j.gastro.2014.07.020","article-title":"Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota in humans and mice","volume":"147","author":"Albenberg","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrmicro3552","article-title":"Gut biogeography of the bacterial microbiota","volume":"14","author":"Donaldson","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1146\/annurev-pathol-012615-044231","article-title":"Hypoxia and Mucosal Inflammation","volume":"11","author":"Colgan","year":"2016","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10493","DOI":"10.1074\/jbc.REV120.011188","article-title":"Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine","volume":"295","author":"Singhal","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1042\/bj3620239","article-title":"Interactions of Porphyromonas gingivalis with oxyhaemoglobin and deoxy-haemoglobin","volume":"362","author":"Smalley","year":"2002","journal-title":"Biochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/omi.12229","article-title":"Potential role for Streptococcus gordonii-derived hydrogen peroxide in heme acquisition by Porphyromonas gingivalis","volume":"33","author":"Brown","year":"2018","journal-title":"Mol. Oral Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fcimb.2019.00233","article-title":"Porphyromonas gingivalis PgFur Is a Member of a Novel Fur Subfamily With Non-canonical Function","volume":"9","author":"Bielecki","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1093\/bib\/bbx108","article-title":"MAFFT online service: Multiple sequence alignment, interactive sequence choice and visualization","volume":"20","author":"Katoh","year":"2019","journal-title":"Briefings Bioinform."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A vis-ualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbrc.2011.06.129","article-title":"Iron(III) mesoporphyrin IX and iron(III) deuteroporphyrin IX bind to the Porphyromonas gingivalis HmuY hemophore","volume":"411","author":"Wojaczynski","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2237\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:27:30Z","timestamp":1760160450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052237"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052237","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]}}}