Receptors for transferrin in pathogenic bacteria are specific for the host's protein

Schryvers, Anthony B.; Gonzalez, Guido C.

doi:10.1139/m90-026

Cited by 94 publications

(58 citation statements)

References 5 publications

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“…Even though there is considerable homology between the transferrins, such as porcine, bovine, sheep, and ovotransferrin, N. meningitidis can discriminate against these non-human-derived transferrins (85,141,144). This correlates well with the role of N. meningitidis as an obligate human pathogen.…”

Section: Iron Availability In the Human Hostmentioning

confidence: 82%

Iron Transport Systems in Neisseria meningitidis

Perkins-Balding

Ratliff-Griffin

Stojiljković

2004

Microbiol Mol Biol Rev

147

146

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SUMMARY Acquisition of iron and iron complexes has long been recognized as a major determinant in the pathogenesis of Neisseria meningitidis. In this review, high-affinity iron uptake systems, which allow meningococci to utilize the human host proteins transferrin, lactoferrin, hemoglobin, and haptoglobin-hemoglobin as sources of essential iron, are described. Classic features of bacterial iron transport systems, such as regulation by the iron-responsive repressor Fur and TonB-dependent transport activity, are discussed, as well as more specific features of meningococcal iron transport. Our current understanding of how N. meningitidis acquires iron from the human host and the vaccine potentials of various components of these iron transport systems are also reviewed.

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Section: Iron Availability In the Human Hostmentioning

confidence: 82%

Iron Transport Systems in Neisseria meningitidis

Perkins-Balding

Ratliff-Griffin

Stojiljković

2004

Microbiol Mol Biol Rev

147

146

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“…Up to now, to our knowledge, it has been reported that bacterial Tf receptors have a strict host specificity and that they bind only Tf from their particular host (35). This is in contrast to mammalian receptors, which can bind Tf from various sources (27).…”

Section: Discussionmentioning

confidence: 93%

“…It has been shown that meningococcal transferrin receptors bind hTf specifically and fail to bind transferrin from other sources (35). In an attempt to determine whether this specificity was characteristic for both N and C lobes of TbpB, the different fusion proteins were tested for their ability to bind HRP-mTf.…”

Section: Resultsmentioning

confidence: 99%

Identification of human transferrin-binding sites within meningococcal transferrin-binding protein B

et al. 1997

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Transferrin-binding protein B (TbpB) from Neisseria meningitidis binds human transferrin (hTf) at the surface of the bacterial cell as part of the iron uptake process. To identify hTf binding sites within the meningococcal TbpB, defined regions of the molecule were produced in Escherichia coli by a translational fusion expression system and the ability of the recombinant proteins (rTbpB) to bind peroxidase-conjugated hTf was characterized by Western blot and dot blot assays. Both the N-terminal domain (amino acids [aa] 2 to 351) and the C-terminal domain (aa 352 to 691) were able to bind hTf, and by a peptide spot synthesis approach, two and five hTf binding sites were identified in the N-and C-terminal domains, respectively. The hTf binding activity of three rTbpB deletion variants constructed within the central region (aa 346 to 543) highlighted the importance of a specific peptide (aa 377 to 394) in the ligand interaction. Taken together, the results indicated that the N-and C-terminal domains bound hTf approximately 10 and 1000 times less, respectively, than the full-length rTbpB (aa 2 to 691), while the central region (aa 346 to 543) had a binding avidity in the same order of magnitude as the C-terminal domain. In contrast with the hTf binding in the N-terminal domain, which was mediated by conformational epitopes, linear determinants seemed to be involved in the hTf binding in the C-terminal domain. The host specificity for transferrin appeared to be mediated by the N-terminal domain of the meningococcal rTbpB rather than the C-terminal domain, since we report that murine Tf binds to the C-terminal domain. Antisera raised to both N-and C-terminal domains were bactericidal for the parent strain, indicating that both domains are accessible at the bacterial surface. We have thus identified hTf binding sites within each domain of the TbpB from N. meningitidis and propose that the Nand C-terminal domains together contribute to the efficient binding of TbpB to hTf with their respective affinities and specificities for determinants of their ligand.

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“…However, infection in these animals does not lead to extensive infection or to rash development 12,13 . Other animal models that have been described for the bacteremia aspect of Neisseria infection take into account the bacterial preference for human transferrin as an iron source 14,15 . Either supplementing human transferrin or expressing it from a transgene results in an increased bacterial load in the blood stream over an extended time period, but this model shows no bacterial adhesion or rash development 16,17 .…”

mentioning

confidence: 99%

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

Melican

Aubey

Duménil

2014

JoVE

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Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream.

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Receptors for transferrin in pathogenic bacteria are specific for the host's protein

Cited by 94 publications

References 5 publications

Iron Transport Systems in Neisseria meningitidis

Iron Transport Systems in Neisseria meningitidis

Identification of human transferrin-binding sites within meningococcal transferrin-binding protein B

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

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