Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O75191 (H. influenzae)
 4,961 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.
 ...
PMID:Neonatal, urogenital isolates of biotype 4 nontypeable Haemophilus influenzae express a variant P6 outer membrane protein molecule. 137 3

Bacteriological and clinical studies on cefodizime (CDZM, THR-221), a new cephem developed by Hoechst AG and Roussel Uclaf, were carried out and the results are summarized below: 1. Against Gram-positive bacteria, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, antibacterial activities of CDZM were similar to those of cefotaxime (CTX), cefazolin, cefotiam and piperacillin. Against Escherichia coli, Klebsiella pneumoniae and Serratia sp., antibacterial activities of CDZM were similar to that of CTX, and superior to those of other tested antibiotics. Especially against Haemophilus influenzae and Branhamella catarrhalis, it showed an excellent antibacterial activity. 2. Although the clinical efficacy was poor in 1 patient with sepsis caused by Salmonella marcescens and in another with cervical lymphadenitis, in 5 patients with upper respiratory tract infection, 4 patients with bronchitis, 6 patients with bronchopneumonia, 18 patients with pneumonia, 5 patients with urinary tract infection and 1 patient with enteritis, the clinical efficacy was excellent or good and the efficacy rate was 95.1% (39/41) including excellent efficacies in 25 cases. 3. Bacteriologically, all identified causative bacteria were eradicated except for 1 case of Salmonella sp., thus the eradication rate was 97.4% (38/39). Especially S. pneumoniae in 10 cases, H. influenzae in 12 cases and B. catarrhalis in 3 cases were eradicated totally. 4. Adverse reactions were studied in 46 cases, and digestive symptoms were observed in 9 cases (diarrhea 5 cases, loose stools 4 cases). Eruption and vascular pain were observed in 1 case each. As digestive symptoms in 9 cases were mild, the treatment were not suspended. In laboratory test values, elevation of GOT, elevation of GPT, elevation of bilirubin, and eosinophilia were observed in 1 case each. Influences on blood coagulation parameters were studied. No change was observed between the beginning and the end of the treatment. From above results, we have concluded that CDZM is a useful and safe antibiotic in pediatrics, administered at a daily dose of 20 mg/kg divided into 3 or 4 doses and administered intravenously.
 ...
PMID:[Bacteriological and clinical studies of cefodizime in pediatrics]. 188 Sep 19

The amino acid sequence T-P-P-T-P-S-P-S is tandemly duplicated in the heavy chain of human immunoglobulin A1 (IgA1), the major antibody in secretions. The bacterial pathogen Streptococcus sanguis, a precursor to dental caries and a cause of bacterial endocarditis, yields IgA protease that cleaves only the Pro-Thr peptide bond in the left duplication, while the type 2 IgA proteases of the genital pathogen Neisseria gonorrhoeae and the respiratory pathogen Haemophilus influenzae cleave only the P-T bond in the right half. We have sequenced the entire S. sanguis iga gene cloned into Escherichia coli. A segment consisting of 20 amino acids tandemly repeated 10 times, of unknown function, occurs near the amino-terminal end of the enzyme encoded in E. coli. Identification of a predicted zinc-binding region in the S. sanguis enzyme and the demonstration that mutations in this region result in production of a catalytically inactive protein support the idea that the enzyme is a metalloprotease. The N. gonorrhoeae and H. influenzae enzymes were earlier shown to be serine-type proteases, while the Bacteroides melaninogenicus IgA protease was shown to be a cysteine-type enzyme. The streptococcal IgA protease amino acid sequence has no significant homology with either of the two previously determined IgA protease sequences, that of type 2 N. gonorrhoeae and type 1 H. influenzae. The differences in both structure and mechanism among these functionally analogous enzymes underscore their role in the infectious process and offer some prospect of therapeutic intervention.
 ...
PMID:Analysis of the immunoglobulin A protease gene of Streptococcus sanguis. 198 65

IgA1 proteases from H. influenzae, N. meningitidis, S. pneumoniae, and S. sanguis were compared with respect to site of cleavage in the IgA1 molecule and EDTA sensitivity. Proteases from S. sanguis and S. pneumoniae cleaved the Pro (227)-Thr (228) bond within the hinge region of the alpha 1 chain and were inhibited by EDTA. H. influenzae IgA1 protease cleaved the Pro (231)-Ser (232) peptide bond. The activity of IgA1 proteases from H. influenzae and N. meningitidis was unaffected by EDTA. Purified and denatured alpha 1 chain was cleaved only in the hinge region. Other component chains of secretory IgA (secretory component, light and J chains) were not susceptible. In addition to IgA1 protease, S. pneumoniae released exo- and endoglycosidases that removed a considerable portion of carbohydrate side chains of IgA1; this activity was absent from crude IgA1 protease preparations of the other three bacterial species. Association in vitro of polymeric IgA1 with SC did not inhibit the degradation of IgA1 proteases. The considerable resistance of secretory IgA to cleavage by IgA1 proteases may be explained in part by the presence of IgA1 protease-neutralizing antibodies in secretory IgA.
 ...
PMID:IgA1 proteases from Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, and Streptococcus sanguis: comparative immunochemical studies. 676 97

Employing a combination of chemical and spectroscopic techniques, the structure of the Haemophilus influenzae type d capsular polysaccharide was found to be leads to 4)-beta-D-GlcNAc-(1 leads to 3)-beta-D-ManNAcA-(1 leads to. L-Alanine, L-serine, and L-threonine, in the molar ratios of approximately 1.0:1.0:0.3, were linked to C-6 of the D-mannosyluronic residue as amides; the (serine + alanine + threonine) to ManNAcA ratio was approximately 0.95:1.0. Removal of the amino acids by mild hydrolysis with sodium hydroxide resulted in a material that was cross-reactive with the native, type d polymer. The base-treated, type d polysaccharide was not observed to cross-react with either the H. influenzae type e or Escherichia coli K7 capsular polysaccharide, both of which are structurally similar to type d.
 ...
PMID:Structural and immunological studies of the Haemophilus influenzae type d capsular polysaccharide. 679 29

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.
 ...
PMID:Mapping of a surface-exposed, conformational epitope of the P6 protein of Haemophilus influenzae. 759 Oct 76

Two-dimensional electrophoresis was applied to the global analysis of the cellular response of Haemophilus influenzae to sulfamethoxazole and trimethoprim, both inhibitors of tetrahydrofolate synthesis. Deregulation of the synthesis rate of 118 proteins, involved in different metabolic pathways, was observed. The regulation of the genes involved in the metabolism of the amino acids methionine, threonine, serine, glycine, and aspartate was investigated in detail by analysis of protein synthesis and Northern hybridization. The results suggested that the synthesis of methionine biosynthetic enzymes in H. influenzae is regulated in a similar fashion as in Escherichia coli. A good correlation between the results obtained by Northern hybridization and quantification of protein synthesis was observed. In contrast to trimethoprim, sulfamethoxazole triggered the increased synthesis of the heat shock proteins DnaK, GroEL, and GroES.
 ...
PMID:Strategies towards a better understanding of antibiotic action: folate pathway inhibition in Haemophilus influenzae as an example. 974 58

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.
 ...
PMID:Gene HI1472 of Haemophilus influenzae Rd is a novel gene involved in DNA repair. 1064 Nov 83

The affinity of [(3)H]benzylpenicillin for penicillin-binding protein (PBP) 3A was reduced in 25 clinical isolates of beta-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae for which the AMP MIC was > or =1.0 microg/ml. The affinities of PBP 3B and PBP 4 were also reduced in some strains. The sequences of the ftsI gene encoding the transpeptidase domain of PBP 3A and/or PBP 3B and of the dacB gene encoding PBP 4 were determined for these strains and compared to those of AMP-susceptible Rd strains. The BLNAR strains were classified into three groups on the basis of deduced amino acid substitutions in the ftsI gene, which is thought to be involved in septal peptidoglycan synthesis. His-517, near the conserved Lys-Thr-Gly (KTG) motif, was substituted for Arg-517 in group I strains (n = 9), and Lys-526 was substituted for Asn-526 in group II strains (n = 12). In group III strains (n = 4), three residues (Met-377, Ser-385, and Leu-389), positioned near the conserved Ser-Ser-Asn (SSN) motif, were replaced with Ile, Thr, and Phe, respectively, in addition to the replacement with Lys-526. The MICs of cephem antibiotics with relatively high affinities for PBP 3A and PBP 3B were higher than those of AMP and meropenem for group III strains. The MICs of beta-lactams for H. influenzae transformants into which the ftsI gene from BLNAR strains was introduced were as high as those for the donors, and PBP 3A and PBP 3B showed decreased affinities for beta-lactams. There was no clear relationship between 7-bp deletions in the dacB gene and AMP susceptibility. Even though mutations in another gene(s) may be involved in beta-lactam resistance, these data indicate that mutations in the ftsI gene are the most important for development of resistance to beta-lactams in BLNAR strains.
 ...
PMID:Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. 1135 13

The sequences of the ftsI gene, encoding the transpeptidase domain of penicillin binding protein (PBP) 3A and/or PBP 3B, which are involved in septal peptidoglycan synthesis, were determined for 108 clinical strains of Haemophilus influenzae with reduced susceptibility to beta-lactam antibiotics with or without beta-lactamase production and were compared to those of the ampicillin-susceptible Rd strain and ampicillin-susceptible clinical isolates. The sequences have 18 different mutation patterns and were classified into two groups on the basis of amino acid substitutions deduced from the nucleotide sequences located between bp 960 and 1618 of the ftsI gene. In group I strains (n = 7), His-517 was substituted for Arg-517. In group II strains (n = 101), Lys-526 was substituted for Asn-526. In subgroup IIa (n = 5; H. influenzae ATCC 49247), the only observed substitution was Lys-526 for Asn-526; in subgroup IIb (n = 56), Val-502 was substituted for Ala-502 (n = 13), along with several other substitutions: Asn-350 for Asp-350 (n = 15), Asn-350 for Asp-350 and Glu-490 for Gly-490 (n = 14), and Asn-350 for Asp-350 and Ser-437 for Ala-437 (n = 5). In subgroup IIc (n = 25), Thr-502 was substituted for Ala-502. In subgroup IId, Val-449 was substituted for Ile-449 (n = 15). The MICs of beta-lactam antibiotics for the 108 strains were to 8 to 16 times the MICs for susceptible strains. The strains, isolated from both adults and children, were analyzed for genetic relationship by pulsed-field gel electrophoresis and by determination of ftsI sequence phylogeny. Both analyses revealed the lack of clonality and the heterogeneity of the strains, but some clusters suggest the spread and/or persistence of a limited number of strains of the same pulsotype and pattern of amino acid substitutions. Reduced susceptibility to beta-lactam, brought about by mutations of the ftsI gene, is becoming a frequent phenomenon, affecting both strains that produce beta-lactamase and those that do not. The level of resistance remains low but opens the way to greater resistance in the future.
 ...
PMID:Diversity of beta-lactam resistance-conferring amino acid substitutions in penicillin-binding protein 3 of Haemophilus influenzae. 1206 76


1 2 Next >>