PMID:22865843

Citation	Balderas, MA, Nobles, CL, Honsa, ES, Alicki, ER and Maresso, AW (2012) Hal Is a Bacillus anthracis heme acquisition protein. J. Bacteriol. 194:5513-21
Abstract	The metal iron is a limiting nutrient for bacteria during infection. Bacillus anthracis, the causative agent of anthrax and a potential weapon of bioterrorism, grows rapidly in mammalian hosts, which suggests that it efficiently attains iron during infection. Recent studies have uncovered both heme (isd) and siderophore-mediated (asb) iron transport pathways in this pathogen. Whereas deletion of the asb genes results in reduced virulence, the loss of three surface components from isd had no effect, thereby leaving open the question of what additional factors in B. anthracis are responsible for iron uptake from the most abundant iron source for mammals, heme. Here, we describe the first functional characterization of bas0520, a gene recently implicated in anthrax disease progression. bas0520 encodes a single near-iron transporter (NEAT) domain and several leucine-rich repeats. The NEAT domain binds heme, despite lacking a stabilizing tyrosine common to the NEAT superfamily of hemoproteins. The NEAT domain also binds hemoglobin and can acquire heme from hemoglobin in solution. Finally, deletion of bas0520 resulted in bacilli unable to grow efficiently on heme or hemoglobin as an iron source and yielded the most significant phenotype relative to that for other putative heme uptake systems, a result that suggests that this protein plays a prominent role in the replication of B. anthracis in hematogenous environments. Thus, we have assigned the name of Hal (heme-acquisition leucine-rich repeat protein) to BAS0520. These studies advance our understanding of heme acquisition by this dangerous pathogen and justify efforts to determine the mechanistic function of this novel protein for vaccine or inhibitor development.
Links	PubMed PMC3458686 Online version:10.1128/JB.00685-12
Keywords	Amino Acid Sequence; Bacillus anthracis/genetics; Bacillus anthracis/growth & development; Bacillus anthracis/metabolism; Culture Media/chemistry; Gene Deletion; Heme/metabolism; Membrane Transport Proteins/genetics; Membrane Transport Proteins/metabolism; Molecular Sequence Data; Protein Binding; Protein Structure, Tertiary; Sequence Alignment
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BACAN:Q81YT0		GO:0044847: iron acquisition by symbiont from host	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Fig. 4	complete CACAO 9105
BACAN:Q81YT0	involved_in	GO:0044002: acquisition of nutrients from host	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

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