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)

The P6 outer membrane protein is a highly conserved molecule which is present on the surface of all strains of Haemophilus influenzae. Sixty strains of nontypeable H. influenzae which caused invasive disease or colonized the female urogenital tract were studied with monoclonal antibodies 7F3 and 4G4, which recognize different surface-exposed epitopes on the P6 molecule. All 60 strains expressed the epitope recognized by 4G4, whereas 47 of 60 strains expressed the epitope recognized by antibody 7F3. The 7F3-nonreactive strains were all biotype 4 and were recovered from the blood of neonates or postpartum women or from the female urogenital tract. The P6 genes from two 7F3-nonreactive strains were cloned, and the nucleotide sequences were determined. Analysis of amino acid sequences, immunoassays with synthetic peptides, and site-directed mutation of the P6 gene indicate that the epitope recognized by antibody 7F3 is conformational and that the sequence Asp-Ile-Thr is critical in maintaining the conformation of the epitope. We conclude that the unusually virulent clone family of biotype 4 strains of nontypeable H. influenzae express a variant P6 molecule which has an alteration in a highly conserved surface-exposed epitope.
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PMID:Neonatal, urogenital isolates of biotype 4 nontypeable Haemophilus influenzae express a variant P6 outer membrane protein molecule. 137 3

Haemophilus influenzae type b was more resistant to killing by lipopolysaccharide (LPS) antibody and complement after growth in defined medium than in conventional broths. Resistance correlated with decreased binding of LPS antibody, as determined by whole-cell enzyme-linked immunosorbent assay. An inhibition radioimmunoassay was used to determine that bacteria grown in defined medium contained about 2.5 times more capsule than bacteria grown in conventional broth. No major differences were noted in the electrophoretic patterns of outer membrane proteins or LPS. The defined medium did not increase the resistance of a capsule-deficient mutant. Resistance and increased encapsulation could be reproduced after growth in conventional broth supplemented with magnesium, glutamic acid, and aspartic acid. Thus, the growth medium may influence the content of capsule on H. influenzae type b, and may in turn, influence the binding and bactericidal activity of LPS antibody to the cells.
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PMID:A chemically defined medium induces resistance to lipopolysaccharide antibody in Haemophilus influenzae type b. 350 85

P6 is an outer membrane protein of Haemophilus influenzae that is antigenically conserved and considered a candidate component of future H. influenzae vaccines. P6 contains a surface-exposed epitope recognized by monoclonal antibody (MAb) 3B9. This epitope has been shown to be distinct from that recognized by the P6-specific MAbs 7F3 and 4G4 in a competitive inhibition enzyme-linked immunosorbent assay (ELISA). MAb 3B9 did not bind to synthetic P6-specific sequential and overlapping hexameric peptides. Five peptides made to correspond to P6 sequences with high probabilities of surface exposure did not inhibit binding of MAb 3B9 to P6. An antiserum to one of the peptides, designated SP66, inhibited binding of MAb 3B9 to P6. A rabbit antiserum to P6 bound to sequential hexameric peptides, Gly-87AsnThrAspGluArgGlyThr-94, which were in the SP66 region of P6. This antiserum inhibited the binding of P6 to MAb 3B9 in a competitive inhibition ELISA. P6 mutations with His and Ala substitutions at residues Thr-88 and Asn-89 still bound MAb 3B9. MAb 3B9 reacted with Escherichia coli OmpA and Salmonella typhimurium OmpA. Sequence comparisons of P6 with these proteins indicated that the residue in the SP66 region responsible for binding is either Gly-87, Asp-90, or Gly-93. Mercaptoethanol reduction abolished MAb 3B9 binding to E. coli OmpA and S. typhimurium OmpA. In these proteins, immediately downstream of the second cysteine, there is an ArgArg dipeptide which is identical to and aligns with Arg-147Arg-148 in P6. This dipeptide has a high probability of surface exposure in P6. Mutagenesis of the Arg-147Arg-148 to an AlaAla dipeptide in P6 abolished binding of MAb 3B9, demonstrating that it was either a portion of the epitope or important in the protein folding necessary for expression of this epitope. This study demonstrates that MAb 3B9 recognizes a conserved conformational determinant on the surface of H. influenzae that is composed of two discontinuous regions of P6.
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PMID:Mapping of a surface-exposed, conformational epitope of the P6 protein of Haemophilus influenzae. 759 Oct 76

The composition of the peptidoglycan of Haemophilus influenzae was determined by analyzing glycopeptides generated by M1 muramidase hydrolysis using high pressure liquid chromatography, fast atom bombardment mass spectrometry, and fast atom bombardment collisionally activated dissociation tandem mass spectrometry, and amino acid analysis. The structures of 17 glycopeptides, representing 96% of the total peptidoglycan, were ascertained. Fifteen glycopeptides resembled species described for Escherichia coli peptidoglycan (Glauner, B., and Schwarz, U. (1983) The Target of Penicillin (Hackenbeck, R., ed), Walter de Gruyter, Berlin pp. 29-34) as compared with 9 in common with Bordetella pertussis (Tuomanen, E., Schwartz, J., Sande, S., Light, K., and Gage, D. (1989) J. Biol. Chem. 264, 11093-11098). Substitutions for L-alanine in the fourth position of the stem peptide included glycine, aspartic acid, and serine. The peptidoglycan was 27% cross-linked, 2% of which formed between diaminopimelic acid residues. No species was identified containing lysyl-arginine residues characteristic of lipoprotein. The peptidoglycan of non-beta-lactamase-mediated antibiotic-resistant H. influenzae differed from that of sensitive strains by an increase in the amount of disaccharide tripeptides and a decrease in 1,6-anhydro dimers. Both changes were transformable properties that changed in a stepwise fashion in parallel with the degree of antibiotic resistance.
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PMID:Composition of the peptidoglycan of Haemophilus influenzae. 850 90

The nucleotide sequences of the quinolone resistance-determining regions of the gyrA and parC genes from five ciprofloxacin-resistant strains of Haemophilus influenzae (MICs, 2 to 32 micrograms/ml) isolated from patients with cystic fibrosis and three ciprofloxacin-susceptible strains of H. influenzae (MICs, < or = 0.1 micrograms/ml) were determined. Four of the five resistant strains possessed at least one amino acid substitution in each of the GyrA and ParC fragments studied. The mutations identified in GyrA were a serine at residue 84 (Ser-84) to Leu or Tyr and Asp-88 to Asn or Tyr. ParC mutations were in positions exactly analogous to those identified in GyrA, namely, Ser-84 to Ile and Glu-88 to Lys. The Glu-88 to Lys ParC substitution was identified only in high-level ciprofloxacin-resistant strains. These mutations have been shown to be the origin of the observed resistance after transformation into ciprofloxacin-susceptible H. influenzae isolates. These results suggest that H. influenzae isolates require at least one amino acid substitution in both GyrA and ParC in order to attain significant levels of resistance to quinolones.
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PMID:Ciprofloxacin-resistant Haemophilus influenzae strains possess mutations in analogous positions of GyrA and ParC. 880 76

Formylation of the initiator methionyl-tRNA by methionyl-tRNA formyltransferase (MTF) is an essential step in initiation of protein synthesis in eubacteria. Here, site-directed mutagenesis was used to identify active site residues of the Haemophilus influenzae MTF. Of the nine residues investigated, only Arg-41, Asn-107, His-109 and Asp-145 were important for the function of the H. influenzae MTF. Replacement of these residues with Ala resulted in a significant reduction in the efficiency of catalysis. Intrinsic fluorescence analysis indicated that this was not due to a defect in N10-formyltetrahydrofolate (fTHF) binding. The Asp-145 and Arg-41 mutations reduced the affinity of the enzyme for the initiator tRNA, whereas the Asn-107 and His-109 mutations affected catalysis but not tRNA binding. Replacement of Arg-41, His-109 and Asp-145 with functionally similar residues also affected the activity of the enzyme. The data suggest that Asn-107, His-109 and Asp-145 are catalytic residues, whereas Arg-41 is involved in tRNA recognition. In the Escherichia coli glycinamide ribonucleotide formyltransferase, which also uses fTHF as the formyl donor, Asn-106, His-108 and Asp-144 participate in the catalytic step. Together, these observations imply that this group of enzymes uses the same basic mechanism in formylating their substrates.
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PMID:Mapping the active site of the Haemophilus influenzae methionyl-tRNA formyltransferase: residues important for catalysis and tRNA binding. 1008 28

A chimeric plasmid, pJPuvr4, consists of a 16.7 kbp Haemophilus influenzae Rd chromosomal DNA insert at the EcoRI site of vector pJ1-8. This plasmid complements the UV and gamma ray sensitivity of the mutant strain MBH4. This plasmid carries the wild type allele of gene uvr4 which was localised to a 3.8 kbp DraI fragment, with an internal EcoRI site. Partial sequencing of the gene and its alignment with the published genome sequence of H. influenzae Rd revealed uvr4 to be HI1472. HI1472 is a putatively identified open reading frame (ORF), which has been assigned no function so far. The partial sequence did show nt database match with 3D exon of N cadherin gene of homosepians and moaA gene of H. influenzae. Cadherins are involved in cell adhesion, cell to cell contact and morphogenesis in homosepians and moaA gene codes for molybdenum biosynthesis subunitA. This report implicates HI1472 of Haemophilus influenzae Rd in DNA repair. Nucleotide sequence obtained for the gene uvr4 was compared with the published sequence of gene HI1472. A wild type strain variation was observed at the 592nd nucleotide position corresponding to a change from aspartic acid to threonine.
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PMID:Gene HI1472 of Haemophilus influenzae Rd is a novel gene involved in DNA repair. 1064 Nov 83

The Hemophilus influenzae Hap adhesin is an autotransporter protein that undergoes an autoproteolytic cleavage event resulting in extracellular release of the adhesin domain (Hap(s)) from the membrane-associated translocator domain (Hap(beta)). Hap autoproteolysis is mediated by Ser(243) and occurs at LN1036-7 and to a lesser extent at more COOH-terminal alternate sites. In the present study, we sought to further define the mechanism of Hap autoproteolysis. Site-directed mutagenesis of residues His(98) and Asp(140) identified a catalytic triad conserved among a subfamily of autotransporters and reminiscent of the SA (chymotrypsin) clan of serine proteases. Amino-terminal amino acid sequencing of histidine-tagged Hap(beta) species and site-directed mutagenesis established that autoproteolysis occurs at LT1046-7, FA1077-8, and FS1067-8, revealing a consensus target sequence for cleavage that consists of ((Q/R)(A/S)X(L/F)) at the P4 through P1 positions. Examination of a recombinant strain co-expressing a Hap derivative lacking all cleavage sites (HapDelta1036-99) and a Hap derivative lacking proteolytic activity (HapS243A) demonstrated that autoproteolysis occurs by an intermolecular mechanism. Kinetic analysis of Hap autoproteolysis in bacteria expressing Hap under control of an inducible promoter demonstrated that autoproteolysis increases as the density of Hap precursor in the outer membrane increases, confirming intermolecular cleavage and suggesting a novel mechanism for regulation of bacterial adherence and microcolony formation.
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PMID:The Hemophilus influenzae Hap autotransporter is a chymotrypsin clan serine protease and undergoes autoproteolysis via an intermolecular mechanism. 1150 35

A search of the gonococcal genome database using the known zinc-binding protein (znuA) sequences from Escherichia coli and Haemophilus influenzae identified an open reading frame encoding a putative gonococcal ZnuA. The consensus amino acid sequence of this open reading frame possessed a characteristic 30-amino acid histidine-rich metal-binding motif (repetitive HDH sequence) containing 43% histidine and 37% aspartic acid and glutamic acid. Subsequently, two adjacent open reading frames with homology to E. coli and H. influenzae znuB and znuC were located upstream of znuA. When partially purified from sonicated cell-free supernatants by CM-Sepharose chromatography, the mature gonococcal ZnuA had an estimated molecular mass of 38 kDa by SDS-PAGE. The presence of a DNA sequence encoding a 19-amino acid signal peptide and the solubility of the mature ZnuA suggested that this protein was located in the periplasm. Inactivation of the Neisseria gonorrhoeae F62 znuA by insertional mutagenesis resulted in a mutant that had a growth rate lower than that of the wild-type parent strain and that required high concentrations of ZnCl2 (> or = 200 microM) for optimal growth. Using a chemically defined agar medium, the gonococcal ZnuA mutant grew only in the presence of Zn(2+), whereas Mg(2+), Ca(2+), Ni(2+), Fe(2+), Cu(2+), Mn(2+) and Cd(2+) had either no effect or were growth inhibitory.
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PMID:Identification and characterization of a high-affinity zinc uptake system in Neisseria gonorrhoeae. 1150 9

Bacteriophage phiKZ is a giant virus that efficiently infects Pseudomonas aeruginosa strains pathogenic to human and, therefore, it is attractive for phage therapy. We present here the complete phiKZ genome sequence and a preliminary analysis of its genome structure. The 280,334 bp genome is a linear, circularly permutated and terminally redundant, A+T-rich double-stranded DNA molecule. The phiKZ DNA has no detectable sequence homology to other viruses and microorganisms, and it does not contain NotI, PstI, SacI, SmaI, XhoI, and XmaIII endonuclease restriction sites. The genome has 306 open reading frames (ORFs) varying in size from 50 to 2237 amino acid residues. According to the orientation of transcription, ORFs are apparently organized into clusters and most have a clockwise direction. The phiKZ genome also encodes six tRNAs specific for Met (AUG), Asn (AAC), Asp (GAC), Leu (TTA), Thr (ACA), and Pro (CCA). A putative promoter sequence containing a TATATTAC block was identified. Most potential stem-loop transcription terminators contain the tetranucleotide UUCG loops. Some genes may be assigned as phage-encoded RNA polymerase subunits. Only 59 phiKZ gene products exhibit similarity to proteins of known function from a diversity of organisms. Most of these conserved gene products, such as dihydrofolate reductase, ribonucleoside diphosphate reductase, thymidylate synthase, thymidylate kinase, and deoxycytidine triphosphate deaminase are involved in nucleotide metabolism. However, no virus-encoded DNA polymerase, DNA replication-associated proteins, or single-stranded DNA-binding protein were found based on amino acid homology, and they may therefore be strongly divergent from known homologous proteins. Fifteen phiKZ gene products show homology to proteins of pathogenic organisms, including Mycobacterium tuberculosis, Haemophilus influenzae, Listeria sp., Rickettsia prowazakeri, and Vibrio cholerae that must be considered before using this phage as a therapeutic agent. The phiKZ coat contains at least 40 polypeptides, and several proteins are cleaved during virus assembly in a way similar to phage T4. Eleven phiKZ-encoded polypeptides are related to proteins of other bacteriphages that infect a variety of hosts. Among these are four gene products that contain a putative intron-encoded endonuclease harboring the H-N-H motif common to many double-stranded DNA phages. These observations provide evidence that phages infecting diverse hosts have had access to a common genetic pool. However, limited homology on the DNA and protein levels indicates that bacteriophage phiKZ represents an evolutionary distinctive branch of the Myoviridae family.
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PMID:The genome of bacteriophage phiKZ of Pseudomonas aeruginosa. 1191 76


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