PPE37 Is Essential for Mycobacterium tuberculosis Heme-Iron Acquisition (HIA), and a Defective PPE37 in Mycobacterium bovis BCG Prevents HIA

, one of the world's leading causes of death, must acquire nutrients, such as iron, from the host to multiply and cause disease. Iron is an essential metal and possesses two different systems to acquire iron from its environment: siderophore-mediated iron acquisition (SMIA) and heme-iron acquisition (HIA), involving uptake and degradation of heme to release ferrous iron. We have discovered that BCG, the tuberculosis vaccine strain, is severely deficient in HIA, and we exploited this phenotypic difference between BCG and to identify genes involved in HIA by complementing BCG's defect with a fosmid library. We identified , an iron-regulated PPE family gene, as being essential for HIA. BCG complemented with exhibits HIA as efficient as that of , achieving robust growth with