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)

Haemophilus influenzae type b (HIb) is the most common cause of bacterial meningitis in children with a mortality rate ranging from 1.6% to 14%. Most patients have a 2-3 day history of symptoms prior to admission. A few have fulminating disease with rapid neurological deterioration. Review of 191 cases of HIb meningitis revealed a mortality rate of 2.1% but all who died had fulminating meningitis (FM). Four of six patients with FM died. FM patients had symptoms for less than 24 hours before rapid neurological deterioration with increased ICP, seizures, coma and/or respiratory arrest. Review of 10 FM cases revealed that on admission, 5 had hypotension, 3 had thrombocytopenia, and 8 had coma. Typical CSF changes were seen in only 7. All fatal cases died within 24 hours. Brain swelling and tonsillar herniation were found at autopsy. SDS-PAGE outer membrane protein subtyping did not show one "killer strain". Animal and autopsy data suggest that diminished CSF outflow and cerebral edema contribute to increased ICP. To improve survival of FM patients, initial treatment must (1) decrease ICP below levels impairing cerebral perfusion, (2) maintain adequate ventilation and blood pressure, and include (3) LP when stable, (4) antibiotics, and (5) close monitoring. Utilizing these principles, two FM patients survived without major sequelae.
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PMID:Fulminating haemophilus influenzae b meningitis. 670 99

The HtrB protein was first identified in Escherichia coli as a protein required for cell viability at high temperature, but its expression was not regulated by temperature. We isolated an htrB homologue from non-typable Haemophilus influenzae strain (NTHi) 2019, which was able to functionally complement the E. coli htrB mutation. The promoter for the NTHi 2019 htrB gene overlaps the promoter for the rfaE gene, and the two genes are divergently transcribed. The deduced amino acid sequence of NTHi 2019 HtrB had 56% homology to E. coli HtrB. In vitro transcription-translation analysis confirmed production of a protein with an apparent molecular mass of 32-33 kDa. Primer extension analysis revealed that htrB was transcribed from a sigma 70-dependent consensus promoter and its expression was not affected by temperature. The expression of htrB and rfaE was 2.5-4 times higher in the NTHi htrB mutant B29 than in the parental strain. In order to study the function of the HtrB protein in Haemophilus, we generated two isogenic htrB mutants by shuttle mutagenesis using a mini-Tn3. The htrB mutants initially showed temperature sensitivity, but they lost the sensitivity after a few passages at 30 degrees C and were able to grow at 37 degrees C. They also showed hypersensitivity to deoxycholate and kanamycin, which persisted on passage. SDS-polyacrylamide gel electrophoresis analysis revealed that the lipo-oligosaccharide (LOS) isolated from these mutants migrated faster than the wild type LOS and its color changed from black to brown as has been described for E. coli htrB mutants. Immunoblotting analysis also showed that the LOS from the htrB mutants lost reactivity to a monoclonal antibody, 6E4, which binds to the wild type NTHi 2019 LOS. Electrospray ionization-mass spectrometry analysis of the O-deacylated LOS oligosaccharide indicated a modification of the core structure characterized in part by a net loss in phosphoethanolamine. Mass spectrometric analysis of the lipid A of the htrB mutant indicated a loss of one or both myristic acid substitutions. These data suggest that HtrB is a multifunctional protein and may play a controlling role in regulating cell responses to various environmental changes.
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PMID:Mutation of the htrB locus of Haemophilus influenzae nontypable strain 2019 is associated with modifications of lipid A and phosphorylation of the lipo-oligosaccharide. 759 70

Two strains of Haemophilus parasuis, namely, the type strain (ATCC 19417) and strain E751, were investigated with respect to iron acquisition. Both strains produced iron-repressible outer membrane proteins and could acquire iron from porcine transferrin but not from porcine lactoferrin. Neither strain used bovine transferrin, and human transferrin was used to only a very limited extent, if at all. In all cases, iron acquisition from transferrin required direct contact between the organisms and the protein. An affinity isolation technique based on biotinylated porcine transferrin plus streptavidin-agarose, followed by SDS-PAGE, allowed the isolation and identification of two potential porcine transferrin binding polypeptides (94 and 60 kDa) from total membranes derived from the type strain grown under iron-restricted conditions but only one (96 kDa) from strain E751. Each of these polypeptides was iron repressible and was not isolated when biotinylated human or bovine transferrin was used instead of biotinylated porcine transferrin. It is concluded that both strains acquire transferrin-bound iron by means of siderophore-independent mechanisms and that the isolated polypeptides represent porcine transferrin receptor components.
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PMID:Contact-dependent acquisition of transferrin-bound iron by two strains of Haemophilus parasuis. 772 56

A Pasteurella haemolytica A1 gene involved in the biosynthesis of a moiety on the core of the lipopolysaccharide molecule has been cloned and characterized. Escherichia coli clones which carry this gene showed an alteration of its lipopolysaccharide migration profile on tricine SDS-PAGE and exhibited resistance to the core-specific phage U3. In addition, lipopolysaccharide extracted from the E. coli clones was recognized by an anti-corespecific antiserum, but not by antiserum specific for the O antigen of P. haemolytica A1 lipopolysaccharide. Nucleotide sequence analysis of the cloned DNA identified an open reading frame (lpsA) coding for a protein of 263 amino acids which showed significant homology with a Haemophilus influenzae type b lipooligosaccharide biosynthesis gene. PCR amplification of genomic DNA, using primers based on the P. haemolytica A1 lpsA sequence, yielded products from only the A biotypes of P. haemolytica.
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PMID:Cloning and characterization of a gene from Pasteurella haemolytica A1 involved in lipopolysaccharide biosynthesis. 778 93

All Haemophilus influenzae strains have an absolute requirement for exogenously supplied haem for aerobic growth. A majority of strains of H. influenzae type b (Hib) produce a 100 kDa protein which binds haem: haemopexin complexes. This 100 kDa haem:haemopexin binding protein, designated HxuA, was originally detected on the Hib cell surface. Monoclonal antibody (mAb)-based analyses revealed that the HxuA protein was also present in soluble form in Hib culture supernatants. This soluble HxuA protein exhibited haem:haemopexin-binding activity in a direct binding assay. Nucleotide sequence analysis of the hxuA gene from Hib strain DL42, together with N-terminal amino acid analysis of HxuA protein purified from Hib culture supernatant, revealed that this protein was synthesized as a 101 kDa precursor with a leader peptide that was removed to yield a 99 kDa protein. Southern blot analysis of chromosomal DNA from four Hib and four non-typeable H. influenzae (NTHI) strains detected the presence of a single band in each strain that hybridized a Hib hxuA gene probe. Subsequent analysis of these NTHI strains showed that all four strains released into culture supernatant a haem:haemopexin-binding protein that migrated in SDS-PAGE at a rate similar or identical to that of the Hib HxuA protein. A Hib hxuA mutant was used to screen an NTHI genomic DNA library and an NTHI gene was cloned that complemented the mutation in this Hib strain. Nucleotide sequence analysis of this NTHI gene revealed that it encoded a protein with 87% identity to the Hib HxuA protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 100 kDa haem:haemopexin-binding protein of Haemophilus influenzae: structure and localization. 781 44

The lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae (NTHi) is an important factor in pathogenesis and virulence. In an attempt to elucidate the genes involved in LOS biosynthesis, we have cloned the rfaE gene from NTHi 2019 by complementing a Salmonella typhimurium rfaE mutant strain with an NTHi 2019 plasmid library. The rfaE mutant synthesizes lipopolysaccharide (LPS) lacking heptose, and the rfaE gene is postulated to be involved in ADP-heptose synthesis. Retransformation with the plasmid containing 4 kb of NTHi DNA isolated from a reconstituted mutant into rfaE mutants gave wild-type LPS phenotypes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis confirmed the conversion of the rfaE mutant LPS to a wild-type LPS phenotype. Sequence analysis of a 2.4-kb BglII fragment revealed two open reading frames. One open reading frame encodes the RfaE protein with a molecular weight of 37.6 kDa, which was confirmed by in vitro transcription and translation, and the other encodes a polypeptide highly homologous to the Escherichia coli HtrB protein. These two genes are transcribed from the same promoter region into opposite directions. Primer extension analysis of the rfaE gene revealed a single transcription start site at 37 bp upstream of the predicted translation start site. The upstream promoter region contained a sequence (TA AAAT) homologous to the -10 region of the bacterial sigma 70-dependent promoters at an appropriate distance (7 bp), but not sequence resembling the consensus sequence of the -35 region was found. These studies demonstrate the ability to use complementation of defined LPS defects in members of the family Enterobacteriaceae to identify LOS synthesis genes in NTHi.
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PMID:Molecular cloning and characterization of the nontypeable Haemophilus influenzae 2019 rfaE gene required for lipopolysaccharide biosynthesis. 786 52

Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF). Antibodies to a 145-kDa minor outer membrane protein (P145) are bactericidal and protect against experimental bacteremia. To determine if P145 is conserved among case-clone strains, case-clone strains were screened for P145 expression. Assays of a large number of colonies of each strain using colony immunoblot revealed colonies reactive with anti-P145 sera in all 17 case-clone strains. P145 was expressed at a low frequency (0.08%-2.2% of colonies) in 14 strains and at a high frequency (> 98%) in 3 strains. Expression of P145 by reactive colonies was confirmed by SDS-PAGE. Also, anti-P145-nonreactive variant colonies of P145-expressing strains were detected in 0.4%-1.5% of colonies. These findings indicate P145 is conserved among BPF case-clone strains and is subject to phase-variable expression.
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PMID:Phase-variable expression of the 145-kDa surface protein of Brazilian purpuric fever case-clone strains of Haemophilus influenzae biogroup aegyptius. 787 25

Outer membrane proteins P2, P4, and P6 and two with molecular masses of 26 and 28 kDa have been purified from a strain of nontypeable Haemophilus influenzae by a preparative form of polyacrylamide gel electrophoresis (PAGE). Outer membrane protein P6, with a molecular mass of 16 kDa (determined by sodium dodecyl sulfate [SDS]-PAGE) was purified by both native PAGE and SDS-PAGE from three strains of nontypeable H. influenzae and one strain of type b H. influenzae. The same conditions were required for purification from each strain. The suitability of proteins isolated by these methods was assessed by studying the immune response of rats immunized with P6 in incomplete Freund's adjuvant into the Peyer's patches. P6 purified by either native PAGE or SDS-PAGE did not differ significantly from P6 purified by gel filtration and anion-exchange chromatography in the ability to enhance pulmonary clearance of live bacteria. This study also investigated the effects of SDS on P2 immunological responses in vivo and the effects of the reagents Zwittergent and sodium lauryl sarcosinate on outer membrane protein lymphocyte-proliferative responses in vitro. It was found that the presence of SDS in the immunization emulsion enhanced the antigen-specific cell-mediated response but suppressed the antigen-specific antibody responses. The presence of residual traces of Zwittergent in an outer membrane protein preparation inhibited antigen-specific cell-mediated proliferation, whereas extraction of outer membrane proteins with sodium lauryl sarcosinate did not inhibit antigen-specific proliferation. These results demonstrate that preparative PAGE is a suitable method for the purification of proteins from the outer membrane of H. influenzae required for investigation of their immunological significance as vaccine candidates and that traces of reagents used during protein purification may play an important role in determining the success of in vivo and in vitro studies.
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PMID:Conservation of immune responses to proteins isolated by preparative polyacrylamide gel electrophoresis from the outer membrane of nontypeable Haemophilus influenzae. 796 Jan 48

A locus involved in the biosynthesis of gonococcal lipooligosaccharide (LOS) has been cloned from gonococcal strain F62. The locus contains five open reading frames. The first and second reading frames are homologous, but not identical, to the fourth and fifth reading frames, respectively. Interposed is an additional reading frame which has distant homology to the Escherichia coli rfaI and rfaI genes, both glucosyl transferases involved in lipopolysaccharide core biosynthesis. The second and fifth reading frames show strong homology to the lex-1 or lic2A gene of Haemophilus influenzae, but do not contain the CAAT repeats found in this gene. Deletions of each of these five genes, of combinations of genes, and of the entire locus were constructed and introduced into parental gonococcal strain F62 by transformation. The LOS phenotypes were then analyzed by SDS-PAGE and reactivity with monoclonal antibodies. Analysis of the gonococcal mutants indicates that four of these genes are the glycosyl transferases that add GalNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1--4 to the substrate Glc beta 1-->4Hep--R of the inner core region. The gene with homology to E. coli rfaI/rfaI is involved with the addition of the alpha-linked galactose residue in the biosynthesis of the alternative LOS structure Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->4Hep-->R. Since these genes encode LOS glycosyl transferases they have been named lgtA, lgtB, lgtC, lgtD, and lgtE. The DNA sequence analysis revealed that lgtA, lgtC, and lgtD contained poly-G tracts, which, in strain F62 were, respectively, 17, 10, and 11 bp. Thus, three of the LOS biosynthetic enzymes are potentially susceptible to premature termination by reading frame changes. It is likely that these structural features are responsible for the high-frequency genetic variation of gonococcal LOS.
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PMID:Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide. 796 93

Colonies of Haemophilus influenzae are heterogeneous in appearance because of phase variation in opacity. The only cell surface component found to have structural variation correlating with differences in opacity was the lipopolysaccharide (LPS). Changes in LPS structure, seen as migration patterns on tricine-SDS-PAGE, appeared to be independent of a previously described mechanism for generating LPS phase variation. The more transparent variants expressing a higher-molecular-weight LPS were serum sensitive and could efficiently colonize the infant rat nasopharynx after intranasal inoculation. In contrast, the fully opaque variant expressing a smaller-molecular-weight LPS was serum resistant, unable to colonize the nasopharynx, and more virulent when intraperitoneally administered. Organisms disseminating into the blood-stream from the nasopharynx changed phenotype from transparent to opaque. These findings demonstrate the potential importance of LPS structures that determine opacity in pathogenesis and colonization of mucosal surfaces.
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PMID:Relationship between colony morphology and the life cycle of Haemophilus influenzae: the contribution of lipopolysaccharide phase variation to pathogenesis. 810 30


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