Figure 1

A schematic of our current understanding of the heme and iron acquisition systems of H. influenzae. Transport across the outer membrane (OM) of iron and heme from various sources is outlined. Heme from hemoglobin (Hg) can be acquired through the TonB-dependent Hgp and Hup proteins [69, 70]. Heme from hemoglobin-haptoglobin complex (HgHp) is acquired through the Hgps [69]. Heme from heme-hemopexin (HmHpx) is acquired through HxuC, and is dependent on the proteins HxuB and HxuA [71, 72]. Acquisition of heme from heme-human serum albumin (HmHSA) is mediated by HxuC independently of HxuB and HxuA [72]. The role of the TonB-dependent receptor proteins HI1369 and HI0113 has not been experimentally determined although we postulate that along with HxuC and Hup they may act as redundant mediators for acquisition of free heme. Acquisition of transferrin-bound iron requires the TonB-dependent protein TbpA and the accessory protein TbpB [17]. Transport systems for other iron sources and PPIX across the OM have not been determined. Transport across the cytoplasmic membrane is less well characterized. The H. influenzae strains appear to have redundant heme and iron ABC transport systems and multiple candidates for these systems have been discovered. HbpA is a periplasmic heme transporter and may deliver heme to the DppBCDF membrane transporter [55]. The Hib hip locus has also been shown to be involved in heme transport [46]. Iron is transported into the cell via HitABC (FbpABC). Mutations of hpbA or hitABC do not abolish utilization of heme and iron respectively, indicating additional cytoplasmic transport mechanisms. Lipoprotein e(P4) has also been shown to involved in heme acquisition although it is not included in this figure since little is known about its mode of action [21].