Binding of human hemoglobin by Haemophilus influenzae

Frangipane, M

doi:10.1016/0378-1097(94)90511-8

Cited by 29 publications

(49 citation statements)

References 13 publications

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“…This binding activity was inhibitable by different animal Hbs but not by globin or heme alone (12). Similar results were obtained in a study of an Hb binding activity of H. influenzae cells (14). Conversely, Lee and Hill (25) VOL.…”

Section: Discussionsupporting

confidence: 74%

“…The Hb utilization system of H. influenzae was shown to be species specific, since the binding of biotinylated human Hb was only partially inhibited by excess unlabeled rat Hb (14). Moreover, neisseriae, strict human pathogens, are able to use only human transferrin, while a bovine pathogen, Actinobacillus pleuropneumonieae, is able to use only bovine transferrin as an iron source (16,40).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the expression of the H. ducreyi Hb receptor gene is regulated by the availability of heme and not iron (12,13). Similarly, the expression of H. influenzae transferrin and Hb receptors was found to be regulated by heme availability (14,31). Previously, we have identified a Fur box sequence in front of the hmbR gene (45).…”

Section: Discussionmentioning

confidence: 99%

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HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation

et al. 1996

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We have recently cloned and characterized the hemoglobin receptor gene from Neisseria meningitidis serogroup C. N. meningitidis cells expressing HmbR protein were able to bind biotinylated hemoglobin, and the binding was specifically inhibited by unlabeled hemoglobin and not heme. The HmbR-mediated hemoglobin binding activity of N. meningitidis cells was shown to be iron regulated. The presence of hemoglobin but not heme in the growth medium stimulated HmbR-mediated hemoglobin binding activity. The efficiency of utilization of different hemoglobins by the HmbR-expressing N. meningitidis cells was shown to be species specific; human hemoglobin was the best source of iron, followed by horse, rat, turkey, dog, mouse, and sheep hemoglobins. The phenotypic characterization of HmbR mutants of some clinical strains of N. meningitidis suggested the existence of two unrelated hemoglobin receptors. The HmbR-unrelated hemoglobin receptor was shown to be identical to Hpu, the hemoglobin-haptoglobin receptor of N. meningitidis. The Hpu-dependent hemoglobin utilization system was not able to distinguish between different sources of hemoglobin; all animal hemoglobins were utilized equally well. HmbR-like genes are also present in N. meningitidis serogroups A and B, Neisseria gonorrhoeae MS11 and FA19, Neisseria perflava, and Neisseria polysaccharea. The hemoglobin receptor genes from N. meningitidis serogroups A and B and N. gonorrhoeae MS11 were cloned, and their nucleotide sequences were determined. The nucleotide sequence identity ranged between 86.5% (for N. meningitidis serogroup B hmbR and MS11 hmbR) and 93.4% (for N. meningitidis serogroup B hmbR and N. meningitidis serogroup C hmbR). The deduced amino acid sequences of these neisserial hemoglobin receptors were also highly related, with overall 84.7% conserved amino acid residues. A stop codon was found in the hmbR gene of N. gonorrhoeae MS11. This strain was still able to use hemoglobin and hemoglobin-haptoglobin complexes as iron sources, indicating that some gonococci may express only the HmbR-independent hemoglobin utilization system.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation

et al. 1996

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“…Haemin acts as an excellent growth supplement for H. influenzae, as it supplies both a source of porphyrin and a rich source of iron. Free haemin is recognized by a specific receptor complex at the outer membrane (Lee, 1992), as are haemin in association with haemoglobin (Frangipane et al, 1994) and haemopexin . In addition, H. influenzae also has the capacity to sequester haem from haemoglobin in association with its carrier protein, haptoglobin (Stull, 1987).…”

Section: Introductionmentioning

confidence: 99%

Characterization of a ferric‐binding protein mutant in Haemophilus influenzae

Kirby

Gray-Owen

Schryvers

1997

Molecular Microbiology

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SummaryFerric-binding proteins (FbpA) have been implicated in the transferrin receptor-mediated iron acquisition pathways of Haemophilus influenzae and Neisseria spp. These proteins are believed to function by shuttling iron from outer membrane transferrin receptors to a specific inner membrane permease complex. However, the role of these proteins has not been conclusively resolved, as attempts at creating isogenic mutants in the fbpA genes of both species have been unsuccessful, prompting the hypothesis that FbpA may play a critical role in H. influenzae and Neisseria spp. This study describes the construction and characterization of an H. influenzae isogenic fbpA mutant. It is demonstrated that this mutant is deficient in its ability to use human transferrin as a sole iron source, even though the strain is still competent for binding human transferrin. It is also demonstrated that this mutant is impaired in its ability to use ferric citrate as an iron source, and grows at a reduced rate relative to wild type in broth supplemented with protoporphyrin rather than haemin.

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“…Haemophilus influenzae expresses multiple systems for heme acquisition, as first shown by Stull (56). Hb and Hb-haptoglo-bin are bound by Hbp proteins (17,22,38,39); hemin is released and transported into the cell by several outer membrane hemin receptors, such as TdhA (3), Hup (39), and Hxu (51). Moraxella catarrhalis exhibits a contact-independent method for hemin uptake in which HumA, an outer membrane receptor, has direct binding affinity for the metalloporphyrin (18).…”

mentioning

confidence: 99%

Passively Released Heme from Hemoglobin and Myoglobin Is a Potential Source of Nutrient Iron for Bordetella bronchiseptica

2007

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Colonization by Bordetella bronchiseptica results in a variety of inflammatory respiratory infections, including canine kennel cough, porcine atrophic rhinitis, and a whooping cough-like disease in humans. For successful colonization, B. bronchiseptica must acquire iron (Fe) from the infected host. A vast amount of Fe within the host is sequestered within heme, a metalloporphyrin which is coordinately bound in hemoglobin and myoglobin. Utilization of hemoglobin and myoglobin as sources of nutrient Fe by B. bronchiseptica requires expression of BhuR, an outer membrane protein. We hypothesize that hemin is acquired by B. bronchiseptica in a BhuR-dependent manner after spontaneous loss of the metalloporphyrin from hemoglobin and/or myoglobin. Sequestration experiments demonstrated that direct contact with hemoglobin or myoglobin was not required to support growth of B. bronchiseptica in an Fe-limiting environment. Mutant myoglobins, each exhibiting a different affinity for heme, were employed to demonstrate that the rate of growth of B. bronchiseptica was directly correlated with the rate at which heme was lost from the hemoprotein. Finally, Escherichia coli cells expressing recombinant BhuR had the capacity to remove hemin from solution. Collectively, these experiments provided strong experimental support for the model that BhuR is a hemin receptor and B. bronchiseptica likely acquires heme during infection after passive loss of the metalloporphyrin from hemoglobin and/or myoglobin. These results also suggest that spontaneous hemin loss by hemoglobin and myoglobin may be a common mechanism by which many pathogenic bacteria acquire heme and heme-bound Fe.

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Binding of human hemoglobin by Haemophilus influenzae

Cited by 29 publications

References 13 publications

HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation

HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation

Characterization of a ferric‐binding protein mutant in Haemophilus influenzae

Passively Released Heme from Hemoglobin and Myoglobin Is a Potential Source of Nutrient Iron for Bordetella bronchiseptica

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