Fig. 9
From: Heme and hemoglobin utilization by Mycobacterium tuberculosis
Model of heme acquisition by M. tuberculosis. PPE36/PE22 and PPE62 are cell surface-accessible proteins of Mtb that bind heme (red octagon) and are anchored in the outer membrane (OM)15. After uptake across the OM, heme is transferred to the periplasmic lipoprotein DppA, possibly with the help of the periplasmic heme-binding protein Rv0265c. DppA probably delivers heme to the DppBCD transporter for uptake across the inner membrane (IM) as shown for other substrate-binding proteins of ABC transporters75,76. PPE37, which was recently shown to be essential for heme utilization in Mtb Erdman, is not depicted since its localization is unknown. Cytoplasmic heme is degraded to mycobilin by the oxygenase MhuD thereby releasing iron (black dot). Heme is degraded in the cytoplasm by the oxygenase MhuD to release iron. MmpL3 and MmpL11, which may be involved in heme efflux, are not depicted since it has not been experimentally validated. The fact that PPE36/PE22, PPE62, and the Dpp transporter are required for heme and hemoglobin utilization by Mtb indicates that these pathways converge at the cell surface of Mtb. Our study indicates that there is an alternate heme uptake pathway mediated by albumin, whose components are not known. However, the mechanism by which heme is released from hemoglobin is unknown. Figure adapted from ref. 15
