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)

Transposon Tn916 was shown to be capable of direct conjugative transfer in broth and membrane matings between strains of Escherichia coli K12 and between E. coli K12 and Haemophilus influenzae type b. Only Tn916 was transferred, but Tn916 donor ability was not itself inheritable by the recipients and seemed to be associated with the presence of Tn916 on a non-conjugative pBR322-derived vector in the original donor strain. Transfer of Tn916 by conjugation was found to be an efficient method for producing insertion mutations in the chromosome of recipient cells. Although such insertions were unstable when the cells were grown under non-selective conditions, it was possible to show that over 40% of the isolated Tn916 insertions in the chromosome of E. coli K12 were in gene(s) concerned with histidine biosynthesis, implying that there is a partial hot-spot for Tn916 insertion on the E. coli K12 chromosome. When a strain of H. influenzae type b was used as a recipient, out of approximately 1500 transconjugants tested, two mutants were isolated with insertions in genes controlling the expression of iron-regulated transferrin-binding proteins. These mutants constitutively produced major 76 kDa and minor 90 kDa proteins which bound transferrin, even when grown under iron-sufficient conditions. Tn916 insertion mutagenesis, following transfer by conjugation, is a convenient method for isolating mutations in genes concerned with iron acquisition by this important human pathogen.
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PMID:Tn916 insertion mutagenesis in Escherichia coli and Haemophilus influenzae type b following conjugative transfer. 131 5

To investigate the mechanisms of iron acquisition in avian haemophili, strains of Haemophilus paragallinarum and H. avium were tested for siderophore production and utilization of transferrin iron for growth. No evidence of siderophore production was detected in either of these species using a functional screening assay. H. paragallinarum, but not strains of H. avium, was able to acquire iron from 30% saturated chicken and turkey transferrins but not from human, porcine, or bovine transferrins. In response to iron limitation, H. paragallinarum expressed four iron-regulated outer-membrane proteins of 53, 62, 66, and 94 kilodaltons (kDa). Only the 53- and 94-kDa proteins were detected in the H. avium strains. Using affinity methods, the 94- and 53-kDa proteins were isolated specifically by chicken or turkey transferrin, indicating that they may be equivalent to transferrin binding proteins (TBP1 and TBP2, respectively) isolated from other bacterial species. The isolation of the 62- and 66-kDa proteins in association with TBP1 and TBP2 under less stringent washing conditions only in H. paragallinarum implicates these proteins in the iron acquisition process.
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PMID:Correlation between the ability of Haemophilus paragallinarum to acquire ovotransferrin-bound iron and the expression of ovotransferrin-specific receptors. 141 95

Haemophilus influenzae is a heme-dependent bacterium. However, little is known of the heme-iron uptake mechanism in this organism. By using a batch ligand affinity chromatography method, a hemin-binding protein of 39,500 molecular weight was isolated from total membranes derived from H. influenzae type b grown under iron-depleted but not under iron-sufficient conditions. Detection of the hemin-binding protein in a whole-cell binding assay demonstrated a surface-exposed location. Competition binding experiments indicated that this hemin-protein interaction was specific, since only hemin or heme-containing proteins, such as human hemoglobin and bovine catalase, but not protoporphyrin IX, iron-loaded human lactoferrin, or transferrin, could abrogate binding. In a limited survey of other H. influenzae strains, an identical hemin-binding protein was isolated, implying that this polypeptide may be structurally and functionally conserved among strains.
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PMID:Isolation of an outer membrane hemin-binding protein of Haemophilus influenzae type b. 154 54

There is now considerable evidence to show that in the Neisseria and Haemophilus species, membrane receptors specific for either transferrin or lactoferrin are involved in the acquisition of iron from these glycoproteins. In Neisseria meningitidis, the transferrin receptor appears to consist of two proteins, one of which (TBP 1) has an M(r) of 95,000 and the other of which (TBP 2) has an M(r) ranging from 68,000 to 85,000, depending on the strain; TBP 2 binds transferrin after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting, but TBP 1 does not do so. The relative contributions of these two proteins to the binding reaction observed with intact cells and to iron uptake are presently unknown. However, they are being considered as potential components of a group B meningococcal vaccine. Analogous higher- and lower-molecular-weight proteins associated with transferrin binding have been found in N. gonorrhoeae and Haemophilus influenzae. Previous work with polyclonal antibodies raised in mice with whole cells of iron-restricted N. meningitidis showed that the meningococcal TBP 2 exhibits considerable antigenic heterogeneity. Here, we report that antiserum against purified TBP 2 from one strain of N. meningitidis cross-reacts on immunoblotting with the TBP 2 of all meningococcal isolates examined, as well as with the TBP 2 of N. gonorrhoeae. This antiserum also cross-reacted with the TBP 2 of several strains of H. influenzae type b, thus showing the presence of common antigenic domains among these functionally equivalent proteins in different pathogens; no cross-reaction was detected with a purified sample of the human transferrin receptor.
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PMID:Common antigenic domains in transferrin-binding protein 2 of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae type b. 158 6

As an adaptation to the iron-limited environment of the host, Haemophilus influenzae has a transferrin receptor-mediated mechanism of iron acquisition such that it can acquire iron directly from human transferrin. The absence of detectable siderophore production and the presence of transferrin binding in a collection of type b and nontypeable H. influenzae strains indicate that the mechanism is widespread in this species. Growth and binding studies have consistently shown that the receptor is specific for human transferrin, which correlates with the host range of this pathogen. Inhibitor experiments indicate that iron regulation of receptor activity is mediated at the gene level. Affinity isolation experiments indicate that, as observed with other bacterial pathogens, the receptor is composed of two iron-repressible outer membrane proteins, transferrin binding proteins 1 and 2.
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PMID:Iron acquisition in Haemophilus influenzae: receptors for human transferrin. 158 35

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 interactions of ruminant transferrins with receptors on bovine isolates of Pasteurella haemolytica and Haemophilus somnus were compared by growth studies and direct and competitive binding assays. Isolates of P. haemolytica were capable of utilizing and binding transferrin from sheep, goat, or cattle, whereas isolates of H. somnus were capable of utilizing and binding only bovine transferrin.
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PMID:Interaction of ruminant transferrins with transferrin receptors in bovine isolates of Pasteurella haemolytica and Haemophilus somnus. 161 64

The quinone antibiotic streptonigrin was used to select mutants of Haemophilus influenzae type b defective in human transferrin binding. Compared with the parent wild-type strain (JKP1), mutant JKP5 was unable to bind transferrin whilst mutant JKP4 showed reduced binding. JKP5 appeared to lack an approximately 72 kDa transferrin-binding protein. Unlike JKP1, neither JKP4 nor JKP5 were able to acquire iron from human transferrin but their ability to use a variety of other iron and haem compounds as iron sources was unaffected. Such mutants should prove useful in further elucidating the mechanism of transferrin iron-acquisition and its contribution to the virulence of H. influenzae.
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PMID:Isolation and characterisation of Haemophilus influenzae type b mutants defective in transferrin-binding and iron assimilation. 203 33

Derivatives of human transferrin (hTf) with removed or modified N-linked oligosaccharides were compared with native hTf with respect to their binding to bacterial hTf receptors from Neisseria meningitidis, N. gonorrhoeae, and Haemophilus influenzae. Partially and fully deglycosylated hTf were prepared by enzymatic deglycosylation with glycopeptidase F and isolated by concanavalin A-Sepharose affinity chromatography. Oligosaccharide-modified hTf was prepared via mild periodate oxidation. Competition and direct binding experiments with the hTf derivatives demonstrated that the hTf oligosaccharides are not essential for binding to the bacterial hTf receptors.
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PMID:N-linked oligosaccharides of human transferrin are not required for binding to bacterial transferrin receptors. 211 77

The specificity by which Haemophilus species acquired iron from transferrin (TF) was investigated. In a plate bioassay H. influenzae used iron bound to human, bovine and rabbit TFs but not mouse, rat, dog, horse, guinea-pig, pig or ovo- TFs or human and bovine lactoferrins. In contrast, H. pleuropneumoniae used iron only from pig TF whilst H. parainfluenzae was unable to utilize iron bound to any of the human or animal TFs tested. The inhibition of growth imposed on H. influenzae type b strain Eagan by the addition of the synthetic iron chelator EDDA to the culture medium was reversed by 30% iron-saturated human TF added directly to the medium but not when the TF was contained inside a dialysis bag. Dot-blotting of whole cells revealed that human TF bound to the surface of bacteria cultured in iron-restricted but not in iron-plentiful media. Incubation of whole bacterial cells in the presence of the proteolytic enzyme trypsin also abolished TF-binding activity, suggesting that the TF receptor was a protein. In competition dot blotting experiments, human and bovine but not rabbit, dog, mouse or guinea-pig TFs blocked the binding of a horseradish peroxidase--human TF conjugate. SDS-PAGE and Western blotting of outer membranes revealed the presence of a TF-binding protein of approximately 72 kDa. These results suggest that the acquisition of TF-bound iron by H. influenzae type b probably involves a direct interaction with an outer-membrane protein which shows some TF-species specificity.
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PMID:Siderophore-independent acquisition of transferrin-bound iron by Haemophilus influenzae type b. 214 16


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