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In response, pathogenic bacteria have evolved mechanisms to acquire iron from host heme.<jats:italic>Bacillus anthracis<\/jats:italic>, the causative agent of anthrax, utilizes secreted hemophores to scavenge heme from host hemoglobin, thereby facilitating iron acquisition from extracellular heme pools and delivery to iron-regulated surface determinant (Isd) proteins covalently attached to the cell wall. However, several Gram-positive pathogens, including<jats:italic>B. anthracis<\/jats:italic>, contain genes that encode near iron transporter (NEAT) proteins that are genomically distant from the genetically linked Isd locus. NEAT domains are protein modules that partake in several functions related to heme transport, including binding heme and hemoglobin. This finding raises interesting questions concerning the relative role of these NEAT proteins, relative to hemophores and the Isd system, in iron uptake. Here, we present evidence that a<jats:italic>B. anthracis<\/jats:italic>S-layer homology (SLH) protein harboring a NEAT domain binds and directionally transfers heme to the Isd system via the cell wall protein IsdC. This finding suggests that the Isd system can receive heme from multiple inputs and may reflect an adaptation of<jats:italic>B. anthracis<\/jats:italic>to changing iron reservoirs during an infection. Understanding the mechanism of heme uptake in pathogenic bacteria is important for the development of novel therapeutics to prevent and treat bacterial infections.<\/jats:p>","DOI":"10.1128\/jb.00054-10","type":"journal-article","created":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T01:12:13Z","timestamp":1272676333000},"page":"3503-3511","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["A<i>Bacillus anthracis<\/i>S-Layer Homology Protein That Binds Heme and Mediates Heme Delivery to IsdC"],"prefix":"10.1128","volume":"192","author":[{"given":"Yael","family":"Tarlovsky","sequence":"first","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Fabian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cell Biology, Rice University, 309 Keck Hall, Houston, Texas 77096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Solomaha","sequence":"additional","affiliation":[{"name":"Biophysics Core Facility, the University of Chicago, 920 E. 58th St., Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Honsa","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Cell Biology, Rice University, 309 Keck Hall, Houston, Texas 77096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony W.","family":"Maresso","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"18499","DOI":"10.1073\/pnas.0607055103","volume":"103","year":"2006","unstructured":"Abergel, R. 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