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)

We previously reported the analysis of recombinant plasmids from Haemophilus influenzae type b (Hib) that lead to modifications of Escherichia coli lipopolysaccharide (LPS) (Y. Abu Kwaik, R. E. McLaughlin, M. A. Apicella, and S. M. Spinola, Mol. Microbiol. 5:2475-2480, 1991). The modified LPS species are recognized by monoclonal antibodies (MAbs) 6E4 and 3F11. MAb 6E4 binds to a stable 2-keto-3-deoxyoctulosonic acid epitope, while MAb 3F11 binds to a Gal beta 1-4GlcNac epitope that phase varies in Hib at a frequency of 2 to 5%. The internal EcoRI fragment containing most of the DNA required for LPS modification in E. coli was used as the target for transposon mutagenesis. Plasmids containing minitransposon m-Tn3(Cm) randomly inserted into the target fragment were transformed into the isogenic Hib strain, and transposon integration into the Hib chromosome was verified by colony hybridization. The lipooligosaccharides of 36 transformants were phenotypically and antigenically characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reactivity with a variety of MAbs that recognize both stable and phase-varying lipooligosaccharide epitopes. The majority of the mutants had altered reactivity with MAb 6E4. With one exception, these mutants retained the ability to express phase-varying epitopes. Analysis of the transformants suggested that the 6E4 epitope was contained on an oligosaccharide chain separate from that of phase-varying epitopes and appeared to be assembled in at least three separate steps.
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PMID:Generation of lipooligosaccharide mutants of Haemophilus influenzae type b. 140 Jan 98

Isolates from 646 consecutive Finnish Haemophilus influenzae type b (Hib) patients with systemic disease, collected before and during large-scale vaccinations with Hib conjugate vaccines, were analyzed by major outer membrane protein (OMP) subtyping, lipopolysaccharide (LPS) serotyping, and biotyping (BT). Strains with OMP-BT-LPS combinations (clones) 1-I-1 and 1c-I-1 disappeared at the same rate as the disease they were associated with. A preferential decrease in the number of isolates of clone 1-II-1 was recorded, whereas the reduction in disease caused by strains of clone 1-II-9 occurred at a lower rate than expected. The latter clone occurred mainly in the most densely populated area of Finland. Strains belonging to all the common Hib clones were isolated from the 16 infants who acquired Hib disease despite being (partially) vaccinated. Thus, Hib clones disappeared during mass vaccination with conjugate vaccines, although at different rates.
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PMID:Changes in the distribution of Haemophilus influenzae type b clones associated with widespread infant vaccination in Finland. 143 Dec 51

The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites. Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase. The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain. The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules'. These observations sparked off an explosion of research. Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like'. Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae.
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PMID:The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity. 147 64

A study recently conducted across Canada showed that 64 of 2,503 clinical isolates of Haemophilus influenzae were resistant to beta-lactams without production of a beta-lactamase (L. D. Tremblay, J. L'Ecuyer, P. Provencher, M. G. Bergeron, and Canadian Study Group, Can. Med. Assoc. J. 143:895-900, 1990). The beta-lactamase-negative strains formed three distinct groups, with ampicillin MICs of 0.5 to 1, 2 to 4, and greater than or equal to 8 micrograms/ml for groups I, II, and III, respectively. We have investigated the mechanisms of resistance for eight strains originating from different infections and geographic areas. These strains were representative of groups I to III. Five strains were nontypeable, two were type B, and one was non-B. Chromosomal DNA extracted from each strain was used to transform the laboratory strain Rd. Transformants were selected on beta-lactam-containing plates and showed the same level of resistance to ampicillin as the donor strains. Differences in outer membrane proteins, porins, and lipopolysaccharide profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) did not change with resistance. Functional analyses of purified porins in artificial lipid bilayer experiments did not explain resistance. Peptidoglycan synthesis was measured by incorporation of [14C]alanine into trichloroacetic acid-insoluble cell wall material in the presence of chloramphenicol. The growth rate and the rate of peptidoglycan synthesis observed for the transformants of the isogenic set did not correlate with resistance. Whole-cell labeling with 125I-penicillin revealed modifications in penicillin-binding proteins (PBPs) among the transformants. In particular, PBPs 3A and 3B (65 and 63 kDa, respectively) showed a decrease in affinity for beta-lactams in all transformants (groups I, II, and III) and correlated with an increased MIC except in the transformant of group III, which showed higher levels of resistance. Partial purification and proteolytic digestion of 125I-penicillin-labeled PBP 3B led to two types of CnBr peptide profiles on SDS-PAGE, the profiles of the transformed strains from groups I and II being different from those of the control group and group III. Finally, electron microscopy revealed a distinct cell filamentation for the group III transformants. These data clearly indicate that changes in PBPs are a common mechanism that results in a significant level of non-beta-lactamase-mediated beta-lactam resistance in H. influenzae despite serotype, origin of isolation, or geographic distribution.
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PMID:Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada. 151 Apr 47

Protein carriers vary in their ability to increase the immunogenicity of poorly immunogenic or T-lymphocyte-independent antigens. We examined one such carrier, the outer membrane protein complex derived from Neisseria meningitidis serogroup B strain B11, in an attempt to determine why this outer membrane protein complex was more immunogenic in young infants and in relevant animal models than two other carriers used in conjugates made with Haemophilus influenzae type b polysaccharide, a T-cell-independent antigen. A single protein of the outer membrane protein complex, the class 2 porin protein, was purified and shown to function as a T-helper lymphocyte carrier protein. Unexpectedly, it was also found to have mitogenic activity for lymphocytes that was not due to lipopolysaccharide. This mitogenic activity appears to date to be unique to this carrier protein of the carrier proteins tested and may contribute to the ability of the H. influenzae type b conjugate vaccine made with the outer membrane protein complex to generate IgG anti-polysaccharide antibody responses in mice and infant monkeys and protective immune responses in infants less than 6 months of age.
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PMID:A vaccine carrier derived from Neisseria meningitidis with mitogenic activity for lymphocytes. 153 34

Freedom from infection is the result of many tiers of immune defenses that harmoniously interact to rid the body of microorganisms and their products, which are perceived as foreign. The ability to distinguish self from nonself is embodied in lymphocytes, which serve both effector and regulatory functions. Through the elaboration of cytokines and immunoglobulins, lymphocytes recruit nonspecific immune effectors, focus their activity, and modulate the intensity of the immune response. The phylogenetically more primitive complement system serves a similar function. Although congenital defects in immune function occur, by far the most common causes of immunodeficiency are acquired and occur in patients treated for cancer with myelosuppressive, cytolytic drugs and in transplant recipients treated with immunosuppressants. HIV infection and malnutrition are responsible for even larger numbers of immunocompromised patients worldwide. The nature and severity of infections that occur as a result of immunodeficiency vary as a function of the immune effector targeted and the degree to which it is dysfunctional. Granulocytopenia is well tolerated unless the absolute number of circulating cells falls below 500/mm3. Profound granulocytopenia and deficits of neutrophil function are often manifest as bacterial or fungal infections. Complement deficiency predisposes to infection with encapsulated bacteria such as pneumococci, meningococci, and Haemophilus influenzae. T cells play such a central role in the immune response that their derangement is associated with susceptibility to almost any potential pathogen. These patients often succumb to mortal opportunistic infections. Recent advances in hybridoma and recombinant DNA technology have provided us with immunologic reagents that enable us to manipulate the immune response. Anti-CD3 monoclonal antibody has permitted salvage of solid organ transplants in well-defined clinical settings. Monoclonal antibodies against TNF-alpha and lipopolysaccharide may alter the consequences of gram-negative sepsis. Alternatively, recombinant cytokines have been associated with clinically significant tumor regression in selected patients, presumably by enhancing the nascent antitumor immune response. The development of immunologic reagents such as these in concert with our growing understanding of the immune system may translate to improved care for immunocompromised patients.
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PMID:Immune function and dysfunction. A primer for the radiologist. 157 Mar 93

The molecular basis of central nervous system invasiveness by Haemophilus influenzae has been studied by using genetically defined mutants and in vivo and in vitro model systems. Capsular polysaccharide and lipopolysaccharide are important microbial determinants of the ability of H. influenzae to traverse the nasopharynx and localize in the cerebrospinal fluid and meninges after bacteremia. The genes for type b capsule confer greater invasive potential than do those for other capsular polysaccharides, although the molecular basis for this is not understood. Mutants have also indicated the role of lipopolysaccharide in enhancing the efficiency of bacterial translocation from the nose to the blood and in facilitating intravascular survival. Organisms that localize successfully in the blood and central nervous system are the progeny of a small fraction of the original challenge inoculum, often a single bacterium.
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PMID:Molecular basis of invasive Haemophilus influenzae type b disease. 158 86

In animal models, the lipopolysaccharide (LPS) from Haemophilus influenzae contributes to all the signs of meningitis associated with living bacteria. However, when tested in vitro, the amount of LPS in cerebrospinal fluid (CSF) in natural disease shows much greater effects on leukocytes than on endothelial permeability. To investigate whether other bacterial components act with LPS to incite meningeal inflammation, animals were challenged intracisternally with H. influenzae lysates. Upon neutralization of endotoxin, leukocytosis was greatly attenuated, but protein accumulation in CSF persisted. Cell wall from H. influenzae induced meningeal inflammation in a pattern opposite to that of LPS. Its ability to induce blood-brain barrier permeability greatly exceeded its ability to induce leukocytosis in vivo. Thus, cell wall, by acting on endothelia, and LPS, by inducing leukocytosis, may cooperate to induce inflammation in H. influenzae meningitis. Optimal reduction of inflammation and tissue damage in meningitis may require agents directed against cell wall as well as LPS.
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PMID:Bacterial components and the pathophysiology of injury to the blood-brain barrier: does cell wall add to the effects of endotoxin in gram-negative meningitis? 158 87

Several chromosomal loci are involved in lipopolysaccharide (LPS) biosynthesis by Haemophilus influenzae. Two of these, lic1 and lic2, contain multiple open-reading frames (ORFs) and include tandem repeats of the tetramer CAAT within and at the 5' end of the coding region of the first ORF in each locus. Variation in the number of repeats of CAAT is involved in the variable expression of LPS epitopes, and genes within these loci are involved in the biosynthesis of these epitopes. lic3 also contains multiple ORFs and the CAAT repeats in the same arrangement as in the other two lic loci. However, in lic3 metabolic functions are encoded by the downstream genes. ORF2 is galE, encoding uridine 5'-diphosphogalactose 4-epimerase, and ORF4 is adk, encoding adenylate kinase. A mutant H. influenzae with a deleted galE gene had an altered LPS when grown on media lacking galactose and was of reduced virulence in infant rats.
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PMID:Molecular biology of phase-variable lipopolysaccharide biosynthesis by Haemophilus influenzae. 158 88

Monoclonal antibodies (MAbs) to the core antigen region of lipopolysaccharide (LPS) of Pseudomonas aeruginosa were produced from mice immunised with whole cells of heat-killed rough mutants of Pseudomonas aeruginosa expressing partial or complete core LPS. MAbs were screened in an enzyme-linked immunosorbent assay (ELISA) against three different antigen cocktails: S-form LPS from three P. aeruginosa strains, R-form LPS from six P. aeruginosa strains and, as a negative control, R-form LPS from Salmonella typhimurium and Escherichia coli. Selected MAbs were subsequently screened against a range of extracted LPS and whole cells from both reference strains and clinical isolates of P. aeruginosa. The antibodies were also screened in ELISA against whole-cell antigens from other Pseudomonas spp. as well as strains of Haemophilus influenzae, Neisseria subflava and Staphylococcus aureus. Five MAbs reacting with the core component of P. aeruginosa LPS were finally selected. Two of these, MAbs 360.7 and 304.1.4, were particularly reactive in immunoblots against unsubstituted core LPS, including that from O-antigenic serotypes of P. aeruginosa. The MAbs also reacted with some of the other Pseudomonas spp., but not with P. cepacia or Xanthomonas (Pseudomonas) maltophilia. Cross-reactivity with whole cells from other bacterial species was minimal or not observed. Reactivity of MAbs with some Staph. aureus strains was observed, and binding to the protein A component was implicated. The reactivity of the MAbs was investigated further by flow cytometry and immunogold electronmicroscopy. The suitability of the MAbs for an immunological assay for detection of P. aeruginosa in respiratory secretions from CF patients is discussed.
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PMID:Production and characterisation of mouse monoclonal antibodies reactive with the lipopolysaccharide core of Pseudomonas aeruginosa. 158 87


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