Conservation and antigenic cross-reactivity of the transferrin-binding proteins of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria meningitidis

Holland, Julie; Parsons, Tina; Hasan, Abdulaziz A.; Cook, Susanna M.; Stevenson, P.; Griffiths, Elwyn; Williams, Paul

doi:10.1099/13500872-142-12-3505

Cited by 18 publications

(14 citation statements)

References 32 publications

(26 reference statements)

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“…[148,150]. Sera from healthy adults recognize Tbp1 and Tbp2, arguing that these proteins are expressed in vivo [150,151]. Consistent with this observation, as assessed by RT-PCR, both proteins are expressed during acute otitis media [152].…”

Section: Iron and Heme Acquisitionsupporting

confidence: 58%

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Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

Rao¹

1999

FEMS Microbiology Reviews

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Non-typable Haemophilus influenzae is a common commensal organism in the human upper respiratory tract and an important cause of localized respiratory tract disease. The pathogenesis of disease begins with bacterial colonization of the nasopharynx, a process that involves establishment on the mucosal surface and evasion of local immune mechanisms. Under the proper circumstances, the organism spreads contiguously to the middle ear, the sinuses, or the lungs, and then stimulates a brisk inflammatory response, producing symptomatic infection. In this review, we summarize our present understanding of the molecular determinants of this sequence of events. Continued investigation of the molecular mechanism of non-typable H. influenzae pathogenicity should facilitate development of novel approaches to the treatment and prevention of H. influenzae disease.

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Section: Iron and Heme Acquisitionsupporting

confidence: 58%

“…Tbp1 is an integral outer membrane protein, while Tbp2 appears to be anchored in the outer membrane via a lipid moiety [149]. Sera from healthy adults recognize Tbp1 and Tbp2, arguing that these proteins are expressed in vivo [150,151]. [148,150].…”

Section: Iron and Heme Acquisitionmentioning

confidence: 99%

Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

Rao¹

1999

FEMS Microbiology Reviews

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“…The surface accessibility and role in virulence of the Hb and transferrin receptors made them early candidates for vaccine development (Afonina et al, 2006; Cornelissen, 2003). The transferrin and Hb receptors of Haemophilus influenza, Neisseria meningitidis , and Neisseria gonorrhoeae were the early focus of such studies (Holland et al, 1996; Lewis et al, 1999; Richardson & Stojiljkovic, 1999; Stevenson, Williams, & Griffiths, 1992; Webb & Cripps, 1999). However, a potential drawback has been the high level of redundancy and phase variation in the transferrin and heme uptake systems (Ekins, Bahrami, Sijercic, Maret, & Niven, 2004; Richardson & Stojiljkovic, 1999, 2001).…”

Section: Heme Uptake and Utilization In Antimicrobial Drug Developmentioning

confidence: 99%

Extracellular Heme Uptake and the Challenges of Bacterial Cell Membranes

Smith¹,

Wilks²

2012

Current Topics in Membranes

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In bacteria, the fine balance of maintaining adequate iron levels while preventing the deleterious effects of excess iron has led to the evolution of sophisticated cellular mechanisms to obtain, store, and regulate iron. Iron uptake provides a significant challenge given its limited bioavailability and need to be transported across the bacterial cell wall and membranes. Pathogenic bacteria have circumvented the iron-availability issue by utilizing the hosts' heme-containing proteins as a source of iron. Once internalized, iron is liberated from the porphyrin enzymatically for cellular processes within the bacterial cell. Heme, a lipophilic and toxic molecule, poses a significant challenge in terms of transport given its chemical reactivity. As such, pathogenic bacteria have evolved sophisticated membrane transporters to coordinate, sequester, and transport heme. Recent advances in the biochemical and structural characterization of the membrane-bound heme transport proteins are discussed in the context of ligand coordination, protein–protein interaction, and heme transfer.

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“…The TbpA proteins are generally highly conserved within a species, while the TbpB proteins tend to be more variable. For N. meningitidis, it was found that the TbpB proteins could be separated into two families based on sequence and antigenicity (28); however, there are common antigenic domains in the TbpB proteins from N. meningitidis, N. gonorrhoeae, H. influenzae, and A. pleuropneumoniae (17,33). Furthermore, TbpBs from N. meningitidis, H. influenzae, and A. pleuropneumoniae have been demonstrated to be protective antigens in various animal challenge models (1,21,22,29).…”

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confidence: 99%

The Transferrin Binding Protein B of Moraxella catarrhalis Elicits Bactericidal Antibodies and Is a Potential Vaccine Antigen

Myers¹,

Yang²,

Du³

et al. 1998

Infect Immun

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The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease. on July 5, 2020 by guest http://iai.asm.org/ Downloaded from FIG. 2. Nucleotide sequences of the promoter regions of M. catarrhalis 4223 tbpA, orf3, and tbpB genes. (A) Putative promoter elements for tbpA, orf3, and tbpB. RBS, ribosome-binding site. (B) Comparison of Fur-binding sites from E. coli (13), N. meningitidis tbpB (20), H. influenzae tbpB (11), and M. catarrhalis 4223 tbpB. Dots indicate residues identical to the E. coli consensus sequence, and underlining indicates dyad symmetry.

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Conservation and antigenic cross-reactivity of the transferrin-binding proteins of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria meningitidis

Cited by 18 publications

References 32 publications

Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

Extracellular Heme Uptake and the Challenges of Bacterial Cell Membranes

The Transferrin Binding Protein B of Moraxella catarrhalis Elicits Bactericidal Antibodies and Is a Potential Vaccine Antigen

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