Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haemophilus influenzae acquires iron from the iron-transporting glycoprotein transferrin via a receptor-mediated process. This involves two outer-membrane transferrin-binding proteins (Tbps) termed Tbp1 and Tbp2 which show considerable preference for the human form of transferrin. Since the Tbps are attracting considerable attention as potential vaccine components, we used transferrin affinity chromatography to examine their conservation amongst 28 H. influenzae type b strains belonging to different outer-membrane-protein subtypes as well as six non-typable strains. Whole cells of all type b and non-typable strains examined bound human transferrin; whilst most strains possessed a Tbp1 of approximately 105 kDa, the molecular mass of Tbp2 varied from 79 to 94 kDa. Antisera raised against affinity-purified native H. influenzae Tbp1/Tbp2 receptor complex cross-reacted on Western blots with the respective Tbps of all the Haemophilus strains examined. When used to probe Neisseria meningitidis Tbps, sera from each of four mice immunized with the Haemophilus Tbp1/2 complex recognized the 68 kDa Tbp2 of N. meningitidis strain B16B6 but not the 78 kDa Tbp2 of N. meningitidis strain 70942. Serum from one mouse also reacted weakly with Tbp1 of strain B16B6. Apart from a weak reaction with the Tbp2 of a serotype 5 strain, this mouse antiserum failed to recognize the Tbps of the porcine pathogen A. pleuropneumoniae. However, a monospecific polyclonal antiserum raised against the denatured Tbp2 of Neisseria meningitidis B16B6 recognized the Tbps of all Haemophilus and Actinobacillus strains examined. Since H. influenzae forms part of the natural flora of the upper respiratory tract, human sera were screened for the presence of antibodies to the Tbps. Sera from healthy adults contained antibodies which recognized both Tbp1 and Tbp2 from H. influenzae but not N. meningitidis. Convalescent sera from meningococcal meningitis patients contained antibodies which, on Western blots, recognized the Tbps2s of both pathogens. These data demonstrate the existence of shared epitopes on the Tbps of H. influenzae, N. meningitidis and A. pleuropneumoniae despite their transferrin species specificity.
 ...
PMID:Conservation and antigenic cross-reactivity of the transferrin-binding proteins of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria meningitidis. 900 13

We have recently cloned and characterized the hemoglobin (Hb) receptor gene, hmbR, from Neisseria meningitidis. To identify additional proteins that are involved in Hb utilization, the N. meningitidis Hb utilization system was reconstituted in Escherichia coli. Five cosmids from N. meningitidis DNA library enabled a heme-requiring (hemA), HmbR-expressing mutant of E. coli to use Hb as both porphyrin and iron source. Nucleotide sequence analysis of DNA fragments subcloned from the Hb-complementing cosmids identified four open reading frames, three of them homologous to Pseudomonas putida, E. coli, and Haemophilus influenzae exbB, exbD, and tonB genes. The N. meningitidis TonB protein is 28.8 to 33.6% identical to other gram-negative TonB proteins, while the N. meningitidis ExbD protein shares between 23.3 and 34.3% identical amino acids with other ExbD and TolR proteins. The N. meningitidis ExbB protein was 24.7 to 36.1% homologous with other gram-negative ExbB and TolQ proteins. Complementation studies indicated that the neisserial Ton system cannot interact with the E. coli FhuA TonB-dependent outer membrane receptor. The N. meningitidis tonB mutant was unable to use Hb, Hb-haptoglobin complexes, transferrin, and lactoferrin as iron sources. Insertion of an antibiotic cassette in the 3' end of the exbD gene produced a leaky phenotype. Efficient usage of heme by N. meningitidis tonB and exbD mutants suggests the existence of a Ton-independent heme utilization mechanism. E. coli complementation studies and the analysis of N. meningitidis hmbR and hpu mutants suggested the existence of another Hb utilization mechanism in this organism.
 ...
PMID:Neisseria meningitidis tonB, exbB, and exbD genes: Ton-dependent utilization of protein-bound iron in Neisseriae. 900 36

The binding of transferrin at the surface of Actinobacillus pleuropneumoniae (A. pp.) is mediated by two proteins of approximately 60 and 100 kDa. The 60 kDa protein has been shown to be highly divergent among different serotypes and to induce a serotype-specific protective immune response. In this study we have characterized the 100 kDa transferrin-binding protein of A. pp. serotype 7 and designated it as TfbB. The tfbB gene was found to be located immediately downstream of the tfbA gene. It was cloned and sequenced, and antibodies raised against the isolated recombinant protein detected, with a constant intensity, a 100 kDa protein in A. pp. serotypes 2, 4, 6, 7, 8, 9, 10 and 11, and a polypeptide of approximately 103 kDa in serotypes 1, 3, 5A and 12. In addition, comparative analysis of the deduced amino acid sequence showed more than 40% identity with the large transferrin-binding proteins of Neisseria meningitidis and Haemophilus influenzae. The TfbB protein was expressed in E. coli outer membranes in a conformation eliciting porcine transferrin-specific binding activity. Sera of pigs immunized with these TfbB-containing E. coli membranes recognized functional membrane-associated TfbB protein whereas no such reaction was observed upon immunization with isolated recombinant TfbB protein. A preliminary animal experiment showed that TfbB-containing outer membrane preparations from recombinant E. coli can reduce significantly the mortality of an A.pp. infection with the homologous strain.
 ...
PMID:Characterization of a large transferrin-binding protein from Actinobacillus pleuropneumoniae serotype 7. 915 35

Since its discovery at the end of the nineteenth century, Moraxella (Branhamella) catarrhalis has undergone several changes of nomenclature and periodic changes in its perceived status as either a commensal or a pathogen. Molecular analysis based on DNA hybridisation or 16S rDNA sequence comparisons has established its phylogenetic position as a member of the Moraxellaceae and shown that it is related more closely to Acinetobacter spp. than to the genus Neisseria in which it was placed formerly. However, confusion with phenotypically similar Neisseria spp. can occur in the routine diagnostic laboratory if appropriate identification tests are not performed. M. catarrhalis is now accepted as the third commonest pathogen of the respiratory tract after Streptococcus pneumoniae and Haemophilus influenzae. It is a significant cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults, especially those with underlying chest disease. Nosocomial spread of infection, especially within respiratory wards, has been reported. Invasive infection is uncommon, but analysis of reports for England and Wales between 1992 and 1995 revealed 89 cases of M. catarrhalis bacteraemia, with the peak incidence in children aged 1-2 years. Carriage rates of M. catarrhalis are high in children and in the elderly, but its role as a commensal organism has probably been overstated in the past. Approximately 90% of strains are now beta-lactamase positive and, given that the first such strain was reported in 1976, this represents a dramatic increase in frequency over the last 20 years which has not been paralleled in any other species. The BRO-1 and BRO-2 beta-lactamase enzymes of M. catarrhalis are found in other Moraxellaceae, but are not related to beta-lactamases of any other species and their origin is therefore unknown. Molecular and typing studies have shown that the M. catarrhalis species is genetically heterogeneous and these methods have aided epidemiological investigation. Studies of factors that may be related to pathogenicity have shown the existence of three serotypes of lipooligosaccharide and the presence of fimbriae and a possible capsule. Some strains are serum-resistant, probably by virtue of interference with complement action, whilst transferrin- and lactoferrin-binding proteins enable the organism to obtain iron from its environment. An antibody response in humans to various M. catarrhalis antigens, including highly conserved outer-membrane proteins, has been demonstrated. Increased understanding of the organism's pathogenic properties and the host response to it may help to identify suitable vaccine targets or lead to other strategies to prevent infection. Whilst it remains, at present, the third most important respiratory pathogen, the impact of immunisation strategies for other organisms may change this position. The speed with which M. catarrhalis acquired beta-lactamase demonstrates the capacity of this organism to surprise us.
 ...
PMID:Moraxella (Branhamella) catarrhalis--clinical and molecular aspects of a rediscovered pathogen. 915 30

The iron repressible nature of Haemophilus influenzae transferrin binding proteins suggests a regulatory role for elemental iron in their expression. The existence of a Haemophilus ferric uptake repressor (Fur) binding motif identified in the promoter region of both tbpA and tbpB further supports this hypothesis. However, a recent study using brain heart infusion growth medium suggested that transferrin binding protein synthesis in H. influenzae was haem-rather than iron-regulated. The present study re-investigates this observation and using a chemically defined medium, we demonstrate that elemental iron haem or protoporphyrin IX can each regulate Haemophilus influenzae transferrin, haemopexin and haemoglobin receptor expression.
 ...
PMID:Elemental iron does repress transferrin, haemopexin and haemoglobin receptor expression in Haemophilus influenzae. 916 1

Unencapsulated Haemophilus influenzae is the second most common etiologic agent of otitis media in children. H. influenzae requires heme for aerobic growth in vitro and is able to utilize hemoglobin and complexes of heme-hemopexin, heme-albumin, and hemoglobin-haptoglobin and ferritransferrin as sources of iron and heme in vitro. Several of the acquisition mechanisms have been characterized and been shown to be heme repressible in vitro. However, little is known about the expression of heme and/or iron acquisition mechanisms during infections in the middle ear. This study was performed to determine if the genes encoding heme and iron acquisition proteins are transcribed during in vivo growth and to compare these findings with those for samples grown in vitro. Reverse transcriptase PCR (RT-PCR) was used to analyze total RNA fractions derived from in vitro- and in vivo-grown H. influenzae. Genes encoding the transferrin-binding proteins TbpA and TbpB, the 100-kDa hemopexin-binding protein HxuA, and the hemoglobin-binding protein HgpA were transcribed during otitis media. Twelve middle ear fluid samples were analyzed by blind RT-PCR to determine the transcriptional status of these genes in H. influenzae during otitis media. Five isolates had transcripts corresponding to tbpA, tbpB, and hxuA. The presence of hgpA transcripts was variable, depending on the presence of hgpA in the genome of the H. influenzae isolate. Samples without H. influenzae gene transcripts contained other etiologic agents commonly causing otitis media. These data demonstrate that H. influenzae iron and/or heme acquisition genes are transcribed during otitis media and suggest that the microenvironment during acute otitis media starves H. influenzae of heme.
 ...
PMID:Transcription of genes encoding iron and heme acquisition proteins of Haemophilus influenzae during acute otitis media. 935 52

The first crystal structure of the iron-transporter ferric ion-binding protein from Haemophilus influenzae (hFBP), at 1.6 A resolution, reveals the structural basis for iron uptake and transport required by several important bacterial pathogens. Paradoxically, although hFBP belongs to a protein superfamily which includes human transferrin, iron binding in hFBP and transferrin appears to have developed independently by convergent evolution. Structural comparison of hFBP with other prokaryotic periplasmic transport proteins and the eukaryotic transferrins suggests that these proteins are related by divergent evolution from an anion-binding common ancestor, not from an iron-binding ancestor. The iron binding site of hFBP incorporates a water and an exogenous phosphate ion as iron ligands and exhibits nearly ideal octahedral metal coordination. FBP is highly conserved, required for virulence, and is a nodal point for free iron uptake in several Gram-negative pathogenic bacteria, thus providing a potential target for broad-spectrum antibacterial drug design against human pathogens such as H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis.
 ...
PMID:Structure of Haemophilus influenzae Fe(+3)-binding protein reveals convergent evolution within a superfamily. 936 Jun 8

Ferric-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.
 ...
PMID:Characterization of a ferric-binding protein mutant in Haemophilus influenzae. 936 22

Airway inflammation during infection is associated with increased transudation of serum proteins and increased production of protein by the airway epithelium. We therefore, assessed whether Haemophilus influenzae infections in patients with chronic bronchitis are associated with increased levels of transferrin and lactoferrin in the sputum compared to uninfected patients. Sputum sol phase and serum samples from 14 infected and 13 uninfected patients with chronic bronchitis and from 12 bronchial asthma patients were included in the study. The median Q-values (the concentration in sputum sol phase/the concentration in serum) x 10(3) of transferrin appeared increased in chronic bronchitis patients with an H. influenzae infection (26.0, n=13) compared to uninfected controls (9.5, n=11) and bronchial asthma patients (4.5, n=6). The ratio of the Q(transferrin)/Q(albumin) was >1 in infected chronic bronchitis patients, indicating local production of transferrin. Growth of H. influenzae was stimulated more in sputum from infected and uninfected patients with chronic bronchitis than in sputum from patients with bronchial asthma. The concentrations of lactoferrin were not significantly different in infected (n=14) and uninfected (n=13) chronic bronchitis patients and bronchial asthma patients (n=12) (median 137.4, 84.6, 87.1 mg x L(-1), respectively). We conclude that in patients with chronic bronchitis with Haemophilus influenzae infections, the levels of transferrin are increased and the levels of lactoferrin are not associated with infections.
 ...
PMID:Iron-binding proteins in sputum of chronic bronchitis patients with Haemophilus influenzae infections. 938 61

The tbpA and tbpB genes encoding the transferrin receptor proteins, TbpA and TbpB, from Pasteurella haemolytica A1 were cloned, sequenced and expressed in Escherichia coli. The genes were organized in a putative operon arrangement of tbpB- tbpA. The tbpB gene was preceded by putative promoter and regulatory sequences, and followed by a 96 base pair intergenic sequence in which no promoter regions were found, suggesting that the two genes are coordinately transcribed. The deduced amino acid sequences of the TbpA and TbpB proteins had regions of homology with the corresponding Neisseria meningitidis, N. gonorrhoeae, Haemophilus influenzae and Actinobacillus pleuropneumoniae Tbp and Lbp proteins. The intact tbpB gene was expressed in a T7 expression system and the resulting recombinant TbpB protein retained the functional bovine transferrin binding characteristics. The availability of the recombinant TbpB enabled us to demonstrate its specificity for ruminant transferrins, its ability to bind both the C-and N-terminal lobes of bovine transferrin and its preference for the iron-loaded form of this protein. Several attempts at expressing the cloned tbpA gene were unsuccessful, suggesting that the product of the gene may be toxic to E. coli.
 ...
PMID:Characterization of the Pasteurella haemolytica transferrin receptor genes and the recombinant receptor proteins. 940 5


<< Previous 1 2 3 4 5 6 7 8 9 Next >>