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Query: UNIPROT:O75191 (H. influenzae)
 4,961 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial strains of Haemophilus species and Streptococcus pneumoniae were examined for synthesis of the enzyme immunoglobulin A1 (IgA1) protease. Of 36 H. influenzae strains examined, 35 produced IgA1 protease; strains included all six capsular types, unencapsulated variants of types b and d, and untypable H. influenzae. Eight Haemophilus strains (non-H. influenzae) were studied, and two produced IgA1 protease. All 10 strains of S. pneumoniae produced IgA1 protease; these strains included 9 different capsular polysaccharide types and 1 untypable strain. Both IgA1 proteases cleaved myeloma IgA1 and secretory IgA but not myeloma IgA2, IgM, or IgG as determined by immunoelectrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that both enzymes cleaved IgA1 myeloma sera, but not IgA2, into two fragments. The apparent molecular weight of the cleaved fragments was dependent both on the apparent molecular weight of the cleaved fragments was dependent both on the specific IgA1 protease assayed and the specific IgA1 substrate utilized. It is postulated that both carbohydrate variation between the IgA1 substrates studied and the ability of S. pneumoniae glycosidases to cleave carbohydrates from glycoprotein offer an explanation for the different fragment sizes observed.
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PMID:Immunoglobulin A1 protease production by Haemophilus influenzae and Streptococcus pneumoniae. 4 Aug 80

Haemophilus influenzae type b acquires transferrin-bound iron via a siderophore-independent mechanism involving direct contact between the human iron-binding glycoprotein and the bacterial cell surface. Evidence has accumulated to show that the transferrin receptor consists of at least two iron-regulated outer membrane transferrin-binding proteins (TBPs), of which one has a molecular mass of around 100 kDa (TBP1) and the other has a molecular mass of 60 to 90 kDa (TBP2). In H. influenzae type b strain Eagan, proteins of 76, 90, and 107 kDa appear to be involved in transferrin binding. To determine whether these TBPs are expressed during growth in vivo, strain Eagan was recovered without subculture from the intraperitoneal cavities of infected infant rats. By using a dot blot assay, outer membranes prepared from these in vivo-grown bacteria, unlike those grown in iron-sufficient broth, bound human transferrin and produced the 76-, 90-, and 107-kDa TBPs. Immunoblotting experiments using convalescent sera from infected rats also revealed the presence of antibodies to the 76- and 90-kDa strain Eagan TBPs. In addition, convalescent sera from three of four patients recovering from H. influenzae type b meningitis contained antibodies to the 90- and 105-kDa TBPs of the corresponding infecting strain. Furthermore, fresh clinical isolates of H. influenzae type b recovered from blood and cerebrospinal fluid showed constitutive expression of the TBPs, which became iron regulated only after prolonged in vitro subculture on iron-sufficient medium. This contrasted with the laboratory-adapted Eagan strain, in which the TBPs remained iron regulated even after animal passage. These findings indicate that the H. influenzae type b transferrin receptor is expressed during experimental animal and human infections.
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PMID:Evidence for in vivo expression of transferrin-binding proteins in Haemophilus influenzae type b. 161 63

The utilization of heme bound to the serum glycoprotein hemopexin by Haemophilus influenzae type b (Hib) strain DL42 requires the presence of the 100-kDa heme:hemopexin-binding protein encoded by the hxuA gene (M. S. Hanson, S. E. Pelzel, J. Latimer, U. Muller-Eberhard, and E. J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). Nucleotide sequence analysis of a 5-kb region immediately upstream from the hxuA gene revealed the presence of two genes, designated hxuC and hxuB, which encoded outer membrane proteins. The 78-kDa HxuC protein had similarity to TonB-dependent outer membrane proteins of other organisms, whereas the 60-kDa HxuB molecule most closely resembled the ShlB protein of Serratia marcescens. A set of three isogenic Hib mutants with cat cartridges inserted individually into their hxuA, hxuB, and hxuC genes was constructed. None of these mutants could utilize heme:hemopexin. The hxuC mutant was also unable to utilize low levels of free heme, whereas both the hxuA and hxuB mutants could utilize free heme. When the wild-type hxuC gene was present in trans, the hxuC mutant regained its ability to utilize low levels of free heme but still could not utilize heme:hemopexin. The hxuA mutant could utilize heme:hemopexin when a functional hxuA gene from a nontypeable H. influenzae strain was present in trans. Complementation analysis using this cloned nontypeable H. influenzae hxuA gene also indicated that the HxuB protein likely functions in the release of soluble HxuA from the Hib cell. These studies indicate that at least two and possible three gene products are required for utilization of heme bound to hemopexin by Hib strain DL42.
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PMID:A gene cluster involved in the utilization of both free heme and heme:hemopexin by Haemophilus influenzae type b. 775 Dec 72

Haemophilus influenzae can utilize iron-loaded human transferrin as an iron source for growth in vitro. H. influenzae tonB mutants, containing a chloramphenicol acetyltransferase gene within their tonB genes, could bind iron-charged human transferrin to their cell surfaces, but they were unable to utilize this serum glycoprotein as the sole source of iron for growth in vitro. In contrast, these tonB mutants were able to utilize an iron chelate (ferric ammonium citrate) for growth. Transformation of a tonB mutant with a plasmid encoding a wild-type H. influenzae tonB gene restored the ability of a tonB mutant to utilize iron-charged human transferrin. These results indicate that the uptake of iron from human transferrin by H. influenzae is a TonB-dependent process.
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PMID:Utilization of transferrin-bound iron by Haemophilus influenzae requires an intact tonB gene. 782 47

Disease due to nontypeable Haemophilus influenzae begins with colonization of the upper respiratory tract mucosa. We recently reported that two surface-exposed high-molecular-weight proteins (HMW1 and HMW2) expressed by a prototypic strain of nontypeable H. influenzae mediate attachment to cultured epithelial cells. In the present study, we examined the nature of the epithelial cell receptor with which HMW1 interacts. Both proteinase K pretreatment and periodate oxidation of epithelial monolayers resulted in a marked decrease in HMW1-mediated binding, suggesting interaction with a glycoprotein structure. Treatment with peptide-N-glycosidase F produced a similar decrease in attachment and thereby provided further evidence for this conclusion. Desialylation of the epithelial cell surface also reduced binding, implying the presence of sialic acid in the receptor structure. Furthermore, lectins specific for terminal alpha 2-3-linked sialic acid were capable of inhibiting HMW1-mediated attachment. In summary, our results indicate that the HMW1 adhesin interacts with a glycoprotein receptor containing N-linked oligosaccharide chains with sialic acid in an alpha 2-3 configuration.
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PMID:The HMW1 adhesin of nontypeable Haemophilus influenzae recognizes sialylated glycoprotein receptors on cultured human epithelial cells. 806 5

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.
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PMID:Conservation and antigenic cross-reactivity of the transferrin-binding proteins of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria meningitidis. 900 13

Although otitis media with effusion is often preceded by an infection of the tympanic cavity, when cultured, many effusions show no culturable bacteria. Based on the hypothesis that the effusion might play a protective role in the course of infection, the influence of this fluid on adhesion of H. influenzae (Hi) type-b strain 770235 and nontypeable H. influenzae (NTHi) strains to buccal epithelial cells was investigated. Effusions were classified as mucoid, seromucoid and serous. Mucoid secretions inhibited adhesion to a significantly greater extent (62%) than did seromucous (52%) and serous effusions (47%) ( P<0.001). The glycoprotein and high-molecular-weight fractions showed similar levels of inhibition. Sialic acid concentration, and, to a lesser extent, protein concentration, correlated with the level of inhibition. Desialylated effusions lost their ability to block bacterial attachment. Thus, middle ear effusion fluid exhibits an inhibitory effect that is due to mucins, which determine viscosity and represent the sialylated high-molecular-weight glycoprotein fraction of the effusion.
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PMID:Mucin in middle ear effusions inhibits attachment of Haemophilus influenzae to mucosal epithelial cells. 1268 86

Many cell types in the airway express the adhesive glycoprotein for leukocytes intercellular adhesion molecule-1 (ICAM-1) constitutively and/or in response to inflammatory stimuli. In this study, we identified functions of ICAM-1 on airway epithelial cells in defense against infection with Haemophilus influenzae. Initial experiments using a mouse model of airway infection in which the bacterial inoculum was mixed with agar beads that localize inflammation in airways demonstrated that ICAM-1 expression was required for efficient clearance of H. influenzae. Airway epithelial cell ICAM-1 expression required few or no leukocytes, suggesting that epithelial cells could be activated directly by interaction with bacteria. Specific inhibition of ICAM-1 function on epithelial cells by orotracheal injection of blocking antibodies resulted in decreased leukocyte recruitment and H. influenzae clearance in the airway. Inhibition of endothelial cell ICAM-1 resulted in a similar decrease in leukocyte recruitment but did not affect bacterial clearance, indicating that epithelial cell ICAM-1 had an additional contribution to airway defense independent of effects on leukocyte migration. To assess this possibility, we used an in vitro model of neutrophil phagocytosis of bacteria and observed significantly greater engulfment of bacteria by neutrophils adherent to epithelial cells expressing ICAM-1 compared with nonadherent neutrophils. Furthermore, bacterial phagocytosis and killing by neutrophils after interaction with epithelial cells were decreased when a blocking antibody inhibited ICAM-1 function. The results indicate that epithelial cell ICAM-1 participates in neutrophil recruitment into the airway, but its most important role in clearance of H. influenzae may be assistance with neutrophil-dependent bacterial killing.
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PMID:Modulation of airway inflammation and bacterial clearance by epithelial cell ICAM-1. 1516 75

One component of the anti-microbial function of lactoferrin (Lf) is its ability to sequester iron from potential pathogens. To overcome this iron limitation, a number of gram-negative bacterial pathogens have developed a mechanism for acquiring iron directly from this host glycoprotein. This mechanism involves surface receptors capable of specifically binding Lf from the host, removing iron and transporting it across the outer membrane. The iron is then bound by a periplasmic iron-binding protein, FbpA, and transported into the cell via an inner membrane complex comprised of FbpB and FbpC. The receptor has been shown to consist of two proteins, LbpA and LbpB. LbpB is bilobed lipoprotein anchored to the outer membrane via fatty acyl groups attached to the N-terminal cysteine. LbpA is a homologue of siderophore receptors, which consist of an N-terminal plug and a C-terminal beta-barrel region. We propose that the receptor proteins, LbpA and LbpB, induce conformational changes in human Lf (hLf) that lower its affinity for iron that binding by FbpA can drive the transport across the outer membrane, a mechanism shared with transferrin (Tf) receptors. The interaction between the receptor proteins and Lf is quite extensive and has been previously studied by using chimeric proteins comprised of Lf & Tf. In an attempt to evaluate the role of FbpA in the transport process, a series of site-directed mutants of FbpA were prepared and used to replace the wild-type protein in the iron acquisition pathway. The mutations were made in the iron-binding and anion-binding ligands of FbpA and were designed to result in altered binding properties. Protein crystallography of the iron-bound form of the Q58L mutant protein revealed that it was in the open conformation with iron coordinated by Y195 and Y196 from the C-terminal domain but not by the other iron-liganding amino acids from the N-terminal domain, H9 and E57. Replacement of the native FbpA in Neisseria meningitidis with wild-type or mutant Haemophilus influenzae FbpAs resulted in a defect in growth on Tf or Lf, suggesting that there may be a barrier to functional expression of H. influenzae FbpAs in Neisseria meningitidis. Thus mutants of the N. meningitidis FbpA are being prepared to replace wild-type protein in order to test their ability to mediate transport from hLf.
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PMID:Lactoferrin receptors in gram-negative bacteria: insights into the iron acquisition process. 1522 71

The Haemophilus influenzae HMW1 adhesin is a high-molecular weight protein that is secreted by the bacterial two-partner secretion pathway and mediates adherence to respiratory epithelium, an essential early step in the pathogenesis of H. influenzae disease. In recent work, we discovered that HMW1 is a glycoprotein and undergoes N-linked glycosylation at multiple asparagine residues with simple hexose units rather than N-acetylated hexose units, revealing an unusual N-glycosidic linkage and suggesting a new glycosyltransferase activity. Glycosylation protects HMW1 against premature degradation during the process of secretion and facilitates HMW1 tethering to the bacterial surface, a prerequisite for HMW1-mediated adherence. In the current study, we establish that the enzyme responsible for glycosylation of HMW1 is a protein called HMW1C, which is encoded by the hmw1 gene cluster and shares homology with a group of bacterial proteins that are generally associated with two-partner secretion systems. In addition, we demonstrate that HMW1C is capable of transferring glucose and galactose to HMW1 and is also able to generate hexose-hexose bonds. Our results define a new family of bacterial glycosyltransferases.
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PMID:The Haemophilus influenzae HMW1C protein is a glycosyltransferase that transfers hexose residues to asparagine sites in the HMW1 adhesin. 2052


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