{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:46:01Z","timestamp":1788482761947,"version":"build-2803163510"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,6,15]],"date-time":"2013-06-15T00:00:00Z","timestamp":1371254400000},"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":[[2013,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Corynebacterium diphtheriae<\/jats:named-content>\n            utilizes hemin and hemoglobin (Hb) as iron sources during growth in iron-depleted environments, and recent studies have shown that the surface-exposed HtaA protein binds both hemin and Hb and also contributes to the utilization of hemin iron. Conserved (CR) domains within HtaA and in the associated hemin-binding protein, HtaB, are required for the ability to bind hemin and Hb. In this study, we identified and characterized two novel genetic loci in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. diphtheriae<\/jats:named-content>\n            that encode factors that bind hemin and Hb. Both genetic systems contain two-gene operons that are transcriptionally regulated by DtxR and iron. The gene products of these operons are ChtA-ChtB and ChtC-CirA (previously DIP0522-DIP0523). The\n            <jats:italic>chtA<\/jats:italic>\n            and\n            <jats:italic>chtB<\/jats:italic>\n            genes are carried on a putative composite transposon associated with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. diphtheriae<\/jats:named-content>\n            isolates that dominated the diphtheria outbreak in the former Soviet Union in the 1990s. ChtA and ChtC each contain a single N-terminal CR domain and exhibit significant sequence similarity to each other but only limited similarity with HtaA. The\n            <jats:italic>chtB<\/jats:italic>\n            and\n            <jats:italic>htaB<\/jats:italic>\n            gene products exhibited a high level of sequence similarity throughout their sequences, and both proteins contain a single CR domain. Whole-cell binding studies as well as protease analysis indicated that all four of the proteins encoded by these two operons are surface exposed, which is consistent with the presence of a transmembrane segment in their C-terminal regions. ChtA, ChtB, and ChtC are able to bind hemin and Hb, with ChtA showing the highest affinity. Site-directed mutagenesis showed that specific tyrosine residues within the ChtA CR domain were critical for hemin and Hb binding. Hemin iron utilization assays using various\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. diphtheriae<\/jats:named-content>\n            mutants indicate that deletion of the\n            <jats:italic>chtA-chtB<\/jats:italic>\n            region and the\n            <jats:italic>chtC<\/jats:italic>\n            gene has no affect on the ability of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. diphtheriae<\/jats:named-content>\n            to use hemin or Hb as iron sources; however, a\n            <jats:italic>chtB htaB<\/jats:italic>\n            double mutant exhibits a significant decrease in hemin iron use, indicating a role in hemin transport for HtaB and ChtB.\n          <\/jats:p>","DOI":"10.1128\/jb.00244-13","type":"journal-article","created":{"date-parts":[[2013,4,13]],"date-time":"2013-04-13T03:17:47Z","timestamp":1365823067000},"page":"2852-2863","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Analysis of Novel Iron-Regulated, Surface-Anchored Hemin-Binding Proteins in Corynebacterium diphtheriae"],"prefix":"10.1128","volume":"195","author":[{"given":"Courtni E.","family":"Allen","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, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Burgos","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, Bethesda, 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, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1016\/S0041-0101(01)00165-9","article-title":"Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century","volume":"39","author":"Collier RJ","year":"2001","unstructured":"CollierRJ. 2001. 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