Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0348321 (Haemophilus)
15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate potential vaccine antigens, Moraxella catarrhalis outer membrane proteins (OMPs) were studied. We have previously shown an OMP to be a target for human IgG and have now further characterised this OMP which appears to have a molecular mass of 84 kDa and to be distinct from the 81-kDa OMP, CopB. Human transferrin was shown to bind the 84-kDa OMP alone. N-terminal sequencing of this OMP and purified M. catarrhalis transferrin binding protein B (TbpB) revealed homology both with each other and with the TbpB of Haemophilus influenzae and Neisseria meningitidis. Adsorption of human anti-serum with purified TbpB from two M. catarrhalis strains abolished or reduced binding of IgG to the 84-kDa OMP from three M. catarrhalis isolates. IgG binding to CopB was unaffected. It is clear that the 84-kDa OMP is distinct from CopB and is a likely homologue of TbpB.
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PMID:Characterisation of an outer membrane protein of Moraxella catarrhalis. 945 93

As an adaptation to the iron-restricted environment of the host, some bacterial pathogens possess iron acquisition pathways mediated by surface receptors that specifically bind transferrin from the host. The receptor is composed of two receptor proteins, TbpA and TbpB, which are both capable of binding to transferrin. Previous studies have demonstrated that affinity isolation of TbpB from Neisseria meningitidis or Haemophilus influenzae with immobilized human transferrin required the homologous TbpA, implicating a TbpA-TbpB interaction. In this study, we demonstrated that TbpA from either species can facilitate isolation of either TbpB, indicating that the TbpA-TbpB interaction is conserved within these species. Extension of these studies to veterinary pathogens in which a TbpA-Tf complex is used to affinity isolate heterologous TbpBs, demonstrated an interaction between the receptor proteins from N. meningitidis and Actinobacillus pleuropneumoniae. Further delineation of the TbpA-TbpB-transferrin interaction with recombinant chimeric N. meningitidis/A. pleuropneumoniae TbpBs has identified a region encoded by the first 1/4 of the tbpB gene which is involved in Tf binding.
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PMID:Biochemical evidence for a conserved interaction between bacterial transferrin binding protein A and transferrin binding protein B. 948 Jul 90

A novel, competitive immunoassay based on time-resolved fluorimetry was developed, and used to measure the serum concentration of bovine transferrin during acute Haemophilus somnus pneumonia. Upper and lower limits of normality were established using serum from healthy cattle (3.72-1.37 mgmL-1). Following experimental infection with Haemophilus somnus, transferrin concentration was depressed in all calves but recovered to pre-infection levels in groups of calves which had either no lesions, or mild lesions at necropsy between 5 and 6 days after infection. In a third group, which developed extensive lesions, the transferrin concentration remained depressed. Transferrin levels remained within the normal range for all calves during the experimental period. Those calves which had low transferrin concentrations pre-infection, developed extensive lung lesions following experimental infection with Haemophilus somnus.
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PMID:Bovine serum transferrin concentration during acute infection with Haemophilus somnus. 963 71

Haemophilus influenzae biogroup aegyptius (H. aegyptius) is the etiological agent of Brazilian purpuric fever (BPF), a recently described pediatric disease that is often fatal. The vascular destruction that occurs in this disease is a distinctive trait, and little is known about the mechanism(s) of the overwhelming purpura fulminans that causes the high mortality associated with this pediatric infection. Iron is an essential micronutrient for nearly all living cells, and the mechanisms used by bacteria to acquire and internalize iron are often associated with virulence. Therefore, the focus of our studies is the molecular characterization of the iron uptake system used by H. aegyptius. Specifically, we are investigating the high-affinity transferrin binding proteins in the bacterial outer membrane, components of ABC transporter systems, and a possible regulatory mechanism for the genes encoding these proteins. A detailed understanding of the molecular nature of the regulatory genetic components and proteins involved in the acquisition of iron will broaden the knowledge of the pathogenesis of the disease caused by H. aegyptius and will also lead to a better understanding of the nature of other infections that affect the vascular system.
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PMID:Molecular and genetic analysis of iron uptake proteins in the brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius. 972 86

Many pathogens of the Pasteurellaceae and Neisseriaceae possess a surface receptor that binds transferrin (Tf) as an initial step in an iron acquisition process. This receptor is comprised of two proteins, transferrin binding protein A (TbpA) and transferrin binding protein B (TbpB). Since the ability to recognize the iron-loaded form of Tf preferentially would be a useful attribute of these receptors, we examined this property in a number of bacterial species. In solid-phase binding assays with isolated membranes, only the receptor from Moraxella catarrhalis was capable of preferentially binding iron-loaded Tf. In a competitive affinity isolation assay which enabled us to resolve TbpA and TbpB, TbpA from all tested species was shown to bind both apo and iron-loaded Tf. Under these assay conditions TbpB from M. catarrhalis, Haemophilus somnus and Pasteurella haemolytica discriminated between apo and holo Tf, whereas TbpB from Neisseria meningitidis showed no discrimination. The ability of TbpB from N. meningitidis to bind iron-saturated hTf preferentially became evident in a TbpA- background or by using recombinant TbpB. In binding assays with recombinant fusion proteins, both intact TbpB and the N-terminal half of TbpB from all the tested species preferentially bound Fe-loaded Tf, indicating that this may be a conserved mechanism by which these organisms optimize their ability to acquire iron.
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PMID:Discrimination between apo and iron-loaded forms of transferrin by transferrin binding protein B and its N-terminal subfragment. 981 20

Moraxella catarrhalis-induced otitis media continues to be a significant cause of infection in young children, prompting increased efforts at identifying effective vaccine antigens. We have previously demonstrated that M. catarrhalis expresses specific outer membrane proteins (OMPs) in response to iron limitation and that this organism can utilize transferrin and lactoferrin for in vitro growth. One of these proteins, which binds human transferrin, is OMP B1. As the human host presents a naturally iron-limited environment, proteins, like OMP B1, which are expressed in response to this nutritional stress are potential vaccine antigens. In this study, we have developed monoclonal antibody (MAb) 11C6, which reacts to a surface-exposed epitope of OMP B1 expressed by M. catarrhalis 7169. This antibody was used to clone ompB1, and sequence analysis suggested that OMP B1 is the M. catarrhalis homologue to the transferrin binding protein B described for pathogenic Neisseriaceae, Haemophilus influenzae, Actinobacillus pleuropneumoniae, and M. catarrhalis. Expression of recombinant OMP B1 on the surface of Escherichia coli confers transferrin binding activity, confirming that this protein is likely involved in iron acquisition. In addition, ompB1 was used to construct an isogenic mutant in M. catarrhalis 7169. This mutant, termed 7169b12, was used as the control in bactericidal assays designed to determine if OMP B1 elicits protective antibodies. In the presence of MAb 11C6 and human complement, wild-type 7169 demonstrated a 99% decline in viability, whereas the ompB1 isogenic mutant was resistant to this bactericidal activity. Further analysis with MAb 11C6 revealed the presence of this OMP B1 epitope on 31% of the clinical isolates tested. These data suggest that OMP B1 is a potential vaccine antigen against M. catarrhalis infections.
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PMID:Use of an isogenic mutant constructed in Moraxella catarrhalis To identify a protective epitope of outer membrane protein B1 defined by monoclonal antibody 11C6. 991 77

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen, and heterogeneity in the surface-exposed immunodominant domains of NTHI proteins is thought to be associated with the failure of an infection to stimulate an immune response that is cross-protective against heterologous NTHI strains. The aim of this study was to assess the vaccine potential of a surface-exposed component of the NTHI human transferrin receptor, TbpB, and to determine if the antibody response elicited was cross-reactive with heterologous strains of NTHI. The efficacy of immunization with a recombinant form of TbpB (rTbpB) was determined by assessing the pulmonary clearance of viable bacteria 4 h after a live challenge with NTHI. There was a significant reduction in the number of viable bacteria in both the bronchoalveolar lavage fluid (34% for the 20-microgram dose and 58% for the 40-microgram dose) and lung homogenates (26% for the 20-microgram dose and 60% for the 40-microgram dose) of rats immunized with rTbpB compared to the control animals. While rTbpB-specific antibodies from immunized rats were nonspecific in the recognition of TbpB from six heterologous NTHI strains on Western blots, these antibodies differed in their ability to block transferrin binding to heterologous strains and to cross-react in bactericidal assays. If bactericidal antibodies are key indicators of the efficacy of the immune response in eliminating NTHI, this data suggests that while immunization with rTbpB stimulates protective responses against the homologous isolate, variability in the recognition of TbpB from heterologous isolates may limit the potential of rTbpB as an NTHI vaccine component.
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PMID:Immunization with recombinant transferrin binding protein B enhances clearance of nontypeable Haemophilus influenzae from the rat lung. 1022 66

Antigenic stimulation from invasive bacterial infections, and the vaccines designed to prevent them, may promote T cell activation and enhancement of HIV-1 replication. Changes in viral load have been correlated with antigen-specific responses. We prospectively determined the impact of immunization with 23-valent pneumococcal vaccine (PVAX) and Haemophilus influenzae type b (Hib)-modified diphtheria toxoid CRM197 (DT) vaccine on HIV-1 replication in recent HIV-1 seroconverters (n = 14; median, 5.5 months from infection; median CD4+ T cells, 535 microl), and correlated results with vaccine-related immune activation. Specific antibody responses, markers of CD4+ T cell activation (transferrin and interleukin 2 receptors), and viral burden were measured at weeks -2 (pre), 0, 1, 2, 6, and 12 after immunization. By week 2, levels of IgG had increased significantly over baseline in both HIV-1-infected patients and HIV-1-seronegative control subjects (n = 9) for each antigen (geometric mean fold rise: PVAX, 10.1 versus 5.3; Hib, 16.0 versus 11.7; and DT, 26.2 versus 24.5, respectively). Despite these vigorous responses to both polysaccharide and protein antigens, HIV-1-infected patients showed limited evidence of CD4+ T cell activation at 1 week, no consistent rise in HIV-1 burden at any point, and no decline in CD4+ T cell number over time. We conclude that recent HIV-1 seroconverters show vigorous humoral responses to vaccine antigens and limited early evidence of T cell activation, but no substantial or sustained increase in viral replication or decline in CD4+ T cell number. Thus, respiratory bacterial vaccines appear immunogenic and safe early in HIV-1 infection.
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PMID:Immune activation and virologic response to immunization in recent HIV type 1 seroconverters. 1038 Nov 72

The Brazilian purpuric fever (BPF) clone of Haemophilus influenzae biogroup aegyptius causes a fatal septicaemic disease, resembling fulminant meningococcal sepsis, in children. When isolate F3031 was grown under iron-limiting conditions, the presence of several iron-regulated proteins of 38-110 kDa was revealed by electrophoretic analysis and a Fur homologue was shown by immunoblotting. Dot-blot assays and immunoblotting indicated that BPF cells bound human transferrin and contained transferrin-binding proteins in the outer membrane. However, the binding activity and the biosynthesis of these proteins were detected even under iron-rich conditions. Immunoblot analysis demonstrated the presence of a periplasmic protein related to the ferric iron-binding protein A (FbpA), the major iron-binding protein described in Neisseria spp. However, the FbpA homologue in strain F3031 was constitutively expressed and was smaller than the periplasmic protein detected in H. influenzae type b strain Eagan. The periplasm of strain F3031 also contained a protein related to the Streptococcus parasanguis FimA protein which recently has been shown to be involved in iron acquisition in Yersinia pestis. Although the Eagan and F3031 FimA homologues had a similar mol. wt, of 31 kDa, the expression of the BPF fimA-like gene was not regulated by the iron concentration of the culture medium.
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PMID:Fur and iron transport proteins in the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius. 1040 13

Pasteurella multocida is the causative agent of fowl cholera and other diseases of production animals. Isolates are classified into five groups based on capsular antigens and into 16 serotypes based on LPS antigens. Strains causing fowl cholera are most frequently designated A:1, A:3 or A:4. Whole cell bacterins can provide some degree of protection, but only against the homologous LPS serotype. There is good evidence that cross-protective antigens are expressed only under in vivo conditions. Empirically derived, live, attenuated vaccines can protect against heterologous serotypes, but because the basis for attenuation is undefined, reversion to virulence is not uncommon. Work in our laboratory is aimed at using a variety of approaches to identify potential protective antigens or virulence genes to be used as candidates for attenuating mutations or as the basis for vaccine antigen delivery systems. The gene encoding an outer membrane protein, Oma87, which is a homologue of the D15 protective antigen of Haemophilus influenzae, was cloned and sequenced. Rabbit antiserum prepared against recombinant Oma87 could passively protect mice against infection. Type 4 fimbriae form the basis of vaccines against ovine footrot and bovine keratoconjunctivitis. We have identified type 4 fimbriae on the surface of P. multocida, purified the fimbrial subunit protein, PtfA, and determined its N-terminal amino acid sequence. Subsequent cloning of the ptfA gene and its inactivation will now be used to assess the importance of type 4 fimbriae in virulence. There has long been anecdotal evidence for the importance of capsule in virulence, but unequivocal genetic evidence for such a role is lacking. We have cloned and characterised the capsule biosynthetic locus in P. multocida A:1 and identified four bex genes involved in capsule transport and genes encoding enzymes involved in the biosynthesis and transfer of the N-acetyl glucosamine and glucuronic acid components of the capsule. It has been suggested that the low concentration of available iron in vivo acts as an environmental cue for expression of cross-protective antigens. Accordingly, we have cloned and characterised the gene encoding transferrin binding protein, Tbpl, so that its role in immunity and virulence can be investigated. Although P. multocida is not normally considered haemolytic, we have observed haemolysis under anaerobic conditions. Standard library construction and screening resulted in the identification of the mesA gene which encodes an esterase enzyme resulting in a haemolytic phenotype under anaerobic conditions. Virulence studies with mesA- mutants were performed to assess its role in pathogenesis. Using a promoterless phoA gene vector system, the cloning of proteins homologous to known surface proteins of other species as well as proteins unique to P. multocida, allowing their potential as vaccine components to be assessed.
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PMID:Candidate vaccine antigens and genes in Pasteurella multocida. 1048 18


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