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Identified virulence factors of Haemophilus: Iron uptake


Hgp (hemoglobin-binding protein)  

Related genes: hgpC;
Keywords: Iron uptake; Heme uptake;
Characteristics:
H. influenzae has an absolute requirement for exogenously supplied heme for aerobic growth. Most of the pathway converting δ-aminolevulinic acid to heme is lost. So H. influenzae has derived several mechanism to use host heme-hemopexin, hemoglobin-haptoglobin as sources of heme iron for growth.
Three hemoglobin- and hemoglobin-haptoglobin binding protein genes, hgpA, hgpB, and hgpC, contain lengths of tetrameric CCAA repeats.
Functions:
Mediates binding of both hemoglobin:haptoglobin complexes and free hemoglobin.
References:
Jin H, et al., 1996. Cloning of a DNA fragment encoding a heme-repressible hemoglobin-binding outer membrane protein from Haemophilus influenzae. Infect. Immun. 64(8):3134-3141.
Jin H, et al., 1999. Characterization of hgpA, a gene encoding a haemoglobin/haemoglobin-haptoglobin-binding protein of Haemophilus influenzae. Microbiology. 145:905-914.
Morton DJ, et al., 1999. Effect of multiple mutations in the hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae type b. Infect. Immun. 67(6):2729-2739.
Ren Z, et al., 1999. Role of CCAA nucleotide repeats in regulation of hemoglobin and hemoglobin-haptoglobin binding protein genes of Haemophilus influenzae. J. Bacteriol. 181(18):5865-5870.


HhuA (hemoglobin:haptoglobin complexes binding protein)  

Related genes: hhuA;
Keywords: Iron uptake; Heme uptake;
Functions:
Similar to HgpA, mediates binding of both hemoglobin:haptoglobin complexes and free hemoglobin.
References:
Maciver I, et al., 1996. Identification of an outer membrane protein involved in utilization of hemoglobin-haptoglobin complexes by nontypeable Haemophilus influenzae. Infect. Immun. 64(9):3703-3712.
Rao VK, et al., 1999. Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae. FEMS Microbiol. Rev. 23(2):99-129.


HitABC  

Related genes: hitA; hitB; hitC;
Keywords: Iron uptake; ABC transporter;
Characteristics:
hitA encodes a periplasmic ferric-binding protein A (FbpA), a high-affinity iron-binding protein belonging to the transferrin superfamily. hitB encodes a cytoplasmic permease. hitC encodes ATP-binding protein.
Functions:
hitABC(fbpABC) operon encodes a periplasmic-binding protein-dependent iron transport system necessary for the utilization of iron bound to transferrin or iron chelates.
References:
Sanders JD, et al., 1994. Identification of a locus involved in the utilization of iron by Haemophilus influenzae. Infect. Immun. 62(10):4515-4525.
Rao VK, et al., 1999. Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae. FEMS Microbiol. Rev. 23(2):99-129.


HxuABC  

Related genes: hxuA; hxuB; hxuC;
Keywords: Iron uptake; Heme uptake;
Characteristics:
HxuA is a 100-kDa protein that binds heme-hemopexin, HxuB is a 60 kDa protein involved in the release of HxuA from the cell surface into the medium, HxuC is involved in the transport of heme within the cell.
Functions:
Using host heme-hemopexin as the source of heme iron for growth.
References:
Hanson MS, et al., 1992. Identification of a genetic locus of Haemophilus influenzae type b necessary for the binding and utilization of heme bound to human hemopexin. Proc. Natl. Acad. Sci. USA. 89(5):1973-1977.
Cope LD, et al., 1995. A gene cluster involved in the utilization of both free heme and heme:hemopexin by Haemophilus influenzae type b. J. Bacteriol. 177(10):2644-2653.
Cope LD, et al., 1994. The 100 kDa haem:haemopexin-binding protein of Haemophilus influenzae: structure and localization. Mol. Microbiol. 13(5):863-873.
Cope LD, et al., 1998. Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae. Infect. Immun. 66(9):4511-4516.
Rao VK, et al., 1999. Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae. FEMS Microbiol. Rev. 23(2):99-129.


Tbp (transferrin-binding protein)  

Related genes: tbpA; tbpB;
Keywords: Iron uptake; Transferrin-binding protein;
Characteristics:
Instead of using siderophores, H. influenzae and other species, such as N. gonorrohoeae and N. meningitidis, express proteins at the their cell surface that specifically bind hot iron-carrying molecules (such as transferrin and lactoferrin) and scavenge iron from these host molecules.
Two H. influenzae iron-repressible transferrin-binding protein called Tbp1 and Tbp2 were identified.
Structure features:
Tbp1 is a TonB-dependent integral outer membrane proteins.
Tbp2 is anchored in the outer membrane via a lipid moiety.
Functions:
Utilizing transferrin as a source of iron.
References:
Gray-Owen SD, Schryvers AB, 1995. Characterization of transferrin binding proteins 1 and 2 in invasive type b and nontypeable strains of Haemophilus influenzae. Infect. Immun. 63(10):3809-3815.
Jarosik GP, et al., 1995. Utilization of transferrin-bound iron by Haemophilus influenzae requires an intact tonB gene. Infect. Immun. 63(2):710-713.
Rao VK, et al., 1999. Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae. FEMS Microbiol. Rev. 23(2):99-129.








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