{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:46:00Z","timestamp":1788482760364,"version":"build-2803163510"},"reference-count":71,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000038","name":"HHS | U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Corynebacterium diphtheriae<\/jats:named-content>\n            utilizes various heme-containing proteins, including hemoglobin (Hb) and the hemoglobin-haptoglobin complex (Hb-Hp), as iron sources during growth in iron-depleted environments. The ability to utilize Hb-Hp as an iron source requires the surface-anchored proteins HtaA and either ChtA or ChtC. The ability to bind hemin, Hb, and Hb-Hp by each of these\n            <jats:named-content content-type=\"genus-species\">C. diphtheriae<\/jats:named-content>\n            proteins requires the previously characterized conserved region (CR) domain. In this study, we identified an Hb-Hp binding protein, HbpA (38.5 kDa), which is involved in the acquisition of hemin iron from Hb-Hp. HbpA was initially identified from total cell lysates as an iron-regulated protein that binds to both Hb and Hb-Hp\n            <jats:italic>in situ<\/jats:italic>\n            . HbpA does not contain a CR domain and has sequence similarity only to homologous proteins present in a limited number of\n            <jats:named-content content-type=\"genus-species\">C. diphtheriae<\/jats:named-content>\n            strains. Transcription of\n            <jats:italic>hbpA<\/jats:italic>\n            is regulated in an iron-dependent manner that is mediated by DtxR, a global iron-dependent regulator. Deletion of\n            <jats:italic>hbpA<\/jats:italic>\n            from\n            <jats:named-content content-type=\"genus-species\">C. diphtheriae<\/jats:named-content>\n            results in a reduced ability to utilize Hb-Hp as an iron source but has little or no effect on the ability to use Hb or hemin as an iron source. Cell fractionation studies showed that HbpA is both secreted into the culture supernatant and associated with the membrane, where its exposure on the bacterial surface allows HbpA to bind Hb and Hb-Hp. The identification and analysis of HbpA enhance our understanding of iron uptake in\n            <jats:named-content content-type=\"genus-species\">C. diphtheriae<\/jats:named-content>\n            and indicate that the acquisition of hemin iron from Hb-Hp may involve a complex mechanism that requires multiple surface proteins.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The ability to utilize host iron sources, such as heme and heme-containing proteins, is essential for many bacterial pathogens to cause disease. In this study, we have identified a novel factor (HbpA) that is crucial for the use of hemin iron from the hemoglobin-haptoglobin complex (Hb-Hp). Hb-Hp is considered one of the primary sources of iron for certain bacterial pathogens. HbpA has no similarity to the previously identified Hb-Hp binding proteins, HtaA and ChtA\/C, and is found only in a limited group of\n            <jats:named-content content-type=\"genus-species\">C. diphtheriae<\/jats:named-content>\n            strains. Understanding the function of HbpA may significantly increase our knowledge of how this important human pathogen can acquire host iron that allows it to survive and cause disease in the human respiratory tract.\n          <\/jats:p>","DOI":"10.1128\/jb.00676-17","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T12:04:00Z","timestamp":1515499440000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Corynebacterium diphtheriae Iron-Regulated Surface Protein HbpA Is Involved in the Utilization of the Hemoglobin-Haptoglobin Complex as an Iron Source"],"prefix":"10.1128","volume":"200","author":[{"given":"Lindsey R.","family":"Lyman","sequence":"first","affiliation":[{"name":"Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"439","article-title":"Corynebacterium diphtheriae infections currently and in the past","volume":"69","author":"Zasada AA","year":"2015","unstructured":"Zasada AA. 2015. 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