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Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      lacks the complete heme biosynthesis pathway and does not utilize siderophores to acquire iron. The exact mechanism of iron extraction from heme in this bacterium is unknown. This study aimed to characterize the\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      HmuS\n                      <jats:sup>Pg<\/jats:sup>\n                      protein and to compare its properties with those of the\n                      <jats:italic>Bacteroides fragilis<\/jats:italic>\n                      homologous protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      UV-visible spectroscopy was used to demonstrate heme binding and follow heme metabolism. Porphyrin levels in bacterial cells and pigment were determined using HPLC or LC-MS, and iron content using atomic absorption spectroscopy or the ferrozine-based method. The influence of the\n                      <jats:italic>\n                        hmuS\n                        <jats:sup>Pg<\/jats:sup>\n                      <\/jats:italic>\n                      gene deletion on the expression of other genes was analyzed using RNA-seq, RT-qPCR, Western blotting, and enzymatic assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although the HmuS\n                      <jats:sup>Pg<\/jats:sup>\n                      contains a domain characteristic of cobaltochelatases and therefore may be assigned to the I class chelatase family, the protein exhibits distinct features. HmuS\n                      <jats:sup>Pg<\/jats:sup>\n                      is a large protein composed of 6 domains and possesses, predicted by structural modeling, two potential heme-binding sites.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , HmuS\n                      <jats:sup>Pg<\/jats:sup>\n                      binds heme. NADH and the inner membrane fraction of\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      stimulate its\n                      <jats:italic>in vitro<\/jats:italic>\n                      engagement in heme metabolism. A significantly smaller amount of PPIX, determined in bacterial cells grown in liquid media and in the pigment deposited on the bacterial cells of the \u0394\n                      <jats:italic>\n                        hmuS\n                        <jats:sup>Pg<\/jats:sup>\n                      <\/jats:italic>\n                      mutant strain, suggests it may have lost the ability to release iron from heme and produce PPIX. Inactivation of the\n                      <jats:italic>\n                        hmuS\n                        <jats:sup>Pg<\/jats:sup>\n                      <\/jats:italic>\n                      gene results in reduced biofilm formation and induces changes in the expression of genes involved in heme uptake and homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      HmuS\n                      <jats:sup>Pg<\/jats:sup>\n                      may be used in heme metabolism under certain\n                      <jats:italic>in vivo<\/jats:italic>\n                      circumstances, where heme is still available, iron is efficiently sequestered by host proteins, and intracellular iron reserves are depleted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1788076","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:55:36Z","timestamp":1779180936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biochemical and functional characterization of Porphyromonas gingivalis HmuS protein reveals its participation in heme metabolism"],"prefix":"10.3389","volume":"17","author":[{"given":"Patryk","family":"Cierpisz","sequence":"first","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw","place":["Wroc\u0142aw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"\u015amiga","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw","place":["Wroc\u0142aw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Tracz","sequence":"additional","affiliation":[{"name":"Laboratory of Mass Spectrometry, Faculty of Biotechnology, University of Wroc\u0142aw","place":["Wroc\u0142aw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronivaldo Rodrigues","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University","place":["Bozeman, MT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"DuBois","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University","place":["Bozeman, MT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Olczak","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biology, Faculty of Biotechnology, University of Wroc\u0142aw","place":["Wroc\u0142aw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.tibs.2006.01.001","article-title":"Chelatases: distort to select?","volume":"31","author":"Al-Karadaghi","year":"2006","journal-title":"Trends Biochem. 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