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 first crystal structure of the iron-transporter ferric ion-binding protein from Haemophilus influenzae (hFBP), at 1.6 A resolution, reveals the structural basis for iron uptake and transport required by several important bacterial pathogens. Paradoxically, although hFBP belongs to a protein superfamily which includes human transferrin, iron binding in hFBP and transferrin appears to have developed independently by convergent evolution. Structural comparison of hFBP with other prokaryotic periplasmic transport proteins and the eukaryotic transferrins suggests that these proteins are related by divergent evolution from an anion-binding common ancestor, not from an iron-binding ancestor. The iron binding site of hFBP incorporates a water and an exogenous phosphate ion as iron ligands and exhibits nearly ideal octahedral metal coordination. FBP is highly conserved, required for virulence, and is a nodal point for free iron uptake in several Gram-negative pathogenic bacteria, thus providing a potential target for broad-spectrum antibacterial drug design against human pathogens such as H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis.
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PMID:Structure of Haemophilus influenzae Fe(+3)-binding protein reveals convergent evolution within a superfamily. 936 Jun 8

Pneumonia is an important cause of morbidity and mortality in the United States. The provision of effective prophylaxis for pneumonia has become a major goal for both public health officials and individual physicians. Prophylaxis for community-acquired pneumonia is pathogen-specific and is directed toward the most common microorganisms that cause it. The 23-valent pneumococcal polysaccharide vaccine; the trivalent influenza vaccine; the Haemophilus b conjugate vaccine; and either trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine are recommended to prevent Streptococcus pneumoniae, influenza viruses, H. influenzae type b, and Pneumocystis carinii respectively. Except for the microorganisms listed above, the prevention of nosocomial pneumonia is not pathogen-specific. Rather, prevention of nosocomial pneumonia requires the use of infection control procedures, including patient and staff education; isolation of patients with highly contagious respiratory pathogens; vigorous hand washing; cleaning and sterilizaton of respiratory equipment; and use of sterile water in nebulizers and humidifiers. It also requires procedures to limit pooling and aspiration of secretions, such as positioning and rotation of the bed-bound patient; frequent suctioning of respiratory secretions using gloves and sterile suction catheters; and limiting enteral alimentation. Finally, selective decontamination of the digestive tract may be considered for intubated patients.
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PMID:Prevention of community-acquired and nosocomial pneumonia. 936 44

In Escherichia coli, flavodoxin is the physiological electron donor for the reductive activation of the enzymes pyruvate formate-lyase, anaerobic ribonucleotide reductase, and B12-dependent methionine synthase. As a basis for studies of the interactions of flavodoxin with methionine synthase, crystal structures of orthorhombic and trigonal forms of oxidized recombinant flavodoxin from E. coli have been determined. The orthorhombic form (space group P2(1)2(1)2(1), a = 126.4, b = 41.10, c = 69.15 A, with two molecules per asymmetric unit) was solved initially by molecular replacement at a resolution of 3.0 A, using coordinates from the structure of the flavodoxin from Synechococcus PCC 7942 (Anacystis nidulans). Data extending to 1.8-A resolution were collected at 140 K and the structure was refined to an Rwork of 0.196 and an Rfree of 0.250 for reflections with I > 0. The final model contains 3,224 non-hydrogen atoms per asymmetric unit, including 62 flavin mononucleotide (FMN) atoms, 354 water molecules, four calcium ions, four sodium ions, two chloride ions, and two Bis-Tris buffer molecules. The structure of the protein in the trigonal form (space group P312, a = 78.83, c = 52.07 A) was solved by molecular replacement using the coordinates from the orthorhombic structure, and was refined with all data from 10.0 to 2.6 A (R = 0.191; Rfree = 0.249). The sequence Tyr 58-Tyr 59, in a bend near the FMN, has so far been found only in the flavodoxins from E. coli and Haemophilus influenzae, and may be important in interactions of flavodoxin with its partners in activation reactions. The tyrosine residues in this bend are influenced by intermolecular contacts and adopt different orientations in the two crystal forms. Structural comparisons with flavodoxins from Synechococcus PCC 7942 and Anaebaena PCC 7120 suggest other residues that may also be critical for recognition by methionine synthase.
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PMID:A flavodoxin that is required for enzyme activation: the structure of oxidized flavodoxin from Escherichia coli at 1.8 A resolution. 941 2

Most prokaryotic (cytosine-5)-DNA methyltransferases increase the frequency of deamination at the cytosine targeted for methylation in vitro in the absence of the cofactor S-adenosylmethionine (AdoMet) or the reaction product S-adenosylhomocysteine (AdoHcy). We show here that, under the same in vitro conditions, the prokaryotic methyltransferase, M.MspI (from Moraxella sp.), causes very few cytosine deaminations, suggesting a mechanism in which M.MspI may avoid enzyme-mediated cytosine deamination. Two analogues of AdoMet, sinefungin and 5'-amino-5'-deoxyadenosine, greatly increased the frequency of cytosine deamination mediated by M.MspI presumably by introducing a proton-donating amino group into the catalytic centre, thus facilitating the formation of an unstable enzyme-dihydrocytosine intermediate and hydrolytic deamination. Interestingly, two naturally occurring analogues, adenosine and 5'-methylthio-5'-deoxyadenosine, which do not contain a proton-donating amino group, also weakly increased the deamination frequency by M.MspI, even in the presence of AdoMet or AdoHcy. These analogues may trigger a conformational change in the enzyme without completely inhibiting the access of solvent water to the catalytic centre, thus allowing hydrolytic deamination of the enzyme-dihydrocytosine intermediate. Under normal physiological conditions the enzymes M.HpaII (from Haemophilus parainfluenzae), M. HhaI (from Haemophilus hemolytica) and M.MspI all increased the in vivo deamination frequency at the target cytosines with comparable efficiency.
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PMID:Enzyme-mediated cytosine deamination by the bacterial methyltransferase M.MspI. 957 71

We performed a prospective observational cohort study of the epidemiology and etiology of nosocomial pneumonia in 358 medical ICU patients in two university-affiliated hospitals. Protected bronchoscopic techniques (protected specimen brush and bronchoalveolar lavage) were used for diagnosis to minimize misclassification. Risk factors for ventilator-associated pneumonia were identified using multiple logistic regression analysis. Twenty-eight cases of pneumonia occurred in 358 patients for a cumulative incidence of 7.8% and incidence rates of 12.5 cases per 1, 000 patient days and 20.5 cases per 1,000 ventilator days. Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Hemophilus species made up 65% of isolates from the lower respiratory tract, whereas only 12.5% of isolates were enteric gram-negative bacilli. Daily surveillance cultures of the nares, oropharynx, trachea, and stomach demonstrated that tracheal colonization preceded ventilator-associated pneumonia in 93.5%, whereas gastric colonization preceded tracheal colonization for only four of 31 (13%) eventual pathogens. By multiple logistic regression, independent risk factors for ventilator- associated pneumonia were admission serum albumin <= 2.2 g/dl (odds ratio [OR] 5.9; 95% confidence interval [CI] 2.0-17.6; p = 0.0013), maximum positive end-expiratory pressure >= 7.5 cm H2O (OR, 4.6; 95% CI, 1.4 to 15.1; p = 0.012), absence of antibiotic therapy (OR, 6.7; 95% CI, 1.8 to 25.3; p = 0.0054), colonization of the upper respiratory tract by respiratory gram-negative bacilli (OR, 3.4; 95% CI, 1.1 to 10.1; p = 0.028), pack-years of smoking (OR, 2.3 for 50 pack-years; 95% CI, 1. 2 to 4.2; p = 0.012), and duration of mechanical ventilation (OR, 3. 4 for 14 d; 95% CI, 1.5 to 7.8; p = 0.0044). Several of these risk factors for ventilator-associated pneumonia appear amenable to intervention.
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PMID:Epidemiology of ventilator-acquired pneumonia based on protected bronchoscopic sampling. 984 76

Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria.
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PMID:The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells. 1003 May 44

The streptogramins are a class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally, but the therapeutic use of the natural compounds is limited because they do not dissolve in water. New semisynthetic derivatives, in particular the injectable streptogramin quinupristin/dalfopristin, offer promise for treating the rising number of infections that are caused by multiply resistant bacteria. The streptogramins consist of two structurally unrelated compounds, group A and group B. The group A compounds are polyunsaturated macrolactones: the group B compounds are cyclic hexadepsipeptides. Modifications of the group B components have been mainly performed on the 3-hydroxypicolinoyl, the 4-dimethylaminophenylalanine and the 4-oxo pipecolinic residues. Semi-synthesis on this third residue led to the water-soluble derivative quinupristin. Water-soluble group A derivatives were obtained by Michael addition of aminothiols to the dehydroproline ring of pristinamycin IIA. Followed by oxidation of the intermediate sulfide into the sulfone derivatives (i.e., dalfopristin). Water-soluble derivatives (both group A and group B) can now be obtained at the industrial scale. Modified group B compounds are now also being produced by mutasynthesis, via disruption of the papA gene. Mutasynthesis has proved particularly useful for producing PIB, the group B component of the oral streptogramin RPR 106972. The streptogramins inhibit bacterial growth by disrupting the translation of mRNA into protein. Both the group A and group B compounds bind to the peptidyltransferase domain of the bacterial ribosome. The group A compounds interfere with the elongation of the polypeptide chain by preventing the binding of aa-tRNA to the ribosome and the formation of peptide bonds, while the B compounds stimulate the dissociation of the peptidyl-tRNA and may also interfere with the release of the completed polypeptide by blocking its access to the channel through which it normally leaves the ribosome. The synergy between the group A and group B compounds appears to result from an enhanced affinity of the group B compounds for the ribosome. Apparently, the group A compound induces a conformational change such that B compound binds with greater affinity. The natural streptogramins are produced as mixtures of the group A and B compounds, the combination of which is a more potent antibacterial agent than either type of compound alone. Whereas the type A or type B compound alone has, in vitro and in animal models of infection, a moderate bacteriostatic activity, the combination of the two has strong bacteriostatic activity and often bactericidal activity. Minimal inhibitory concentrations of quinupristin/dalfopristin range from 0.20 to 1 mg/l for Streptococcus pneumonae, from 0.25 to 2 mg/l for Staphylococcus aureus and from 0.50 to 4 for Enterococcus faecium, the principal target organisms of this drug. Quinupristin/dalfopristin also has activity against mycoplasmas, Neisseria gonorrhoeae, Haemophilus influenz, Legionella spp. and Moraxella catarrhalis. Bacteria develop resistance to the streptogramms by ribosomal modification, by producing inactivating enzymes, or by causing an efflux of the antibiotic. Dimethylation of an adenine residue in rRNA, a reaction that is catalyzed by a methylase encoded by the erm gene class, affects the binding of group B compounds (as well as the macrolides and lincosamides; hence, MLSB resistance), but group A and B compounds usually maintain their synergy and their bactericidal effect against MLSB-resistant strains. erm genes are widespread both geographically and throughout numerous bacterial genera. Several types of enzymes (acetyltransferases, hydrolases) have been identified that inactivate the group A or the group B compounds. Genes involved in streptogramin efflux have so far been found only in staphylococci, particularly in coagulase-negative species
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PMID:Recent developments in streptogramin research. 1019 38

IgA nephropathy (IgAN) was first reported by Berger in 1968, and characterized by diffuse IgA deposition in the mesangium. Patients with IgAN have usually episodic macroscopic hematuria accompanied with pharyngitis, gastroenteritis, bronchitis, or sinusitis. These findings suggest that IgAN is an immune-complex disease resulting from a poorly controlled mucosal immune response to environmental antigens to which the patient was chronically exposed. We reported the glomerular deposition of the outer membrane of Haemophilus parainfluenzae (OMHP) antigens and the presence of IgA antibody against OMHP in the sera of patients with IgAN. These suggest that Haemophilus parainfluenzae plays a role in the aetiology of this disease. This study was conducted to determine whether OMHP antigens induced immunohistologically evident glomerular deposition of IgA and C3 in C3H/HeN mice. Female C3H/HeN mice (4 weeks old) received intraperitoneal injection (HP-IP group), and oral administration (HP-PO group) of OMHP antigens. The control group similarly received intraperitoneal injection of PBS, and oral intake of ordinary water. The mice were sacrificed at 10, 20, 30, 40, 50 weeks after the start of the experiment. The HP-IP group showed glomerular deposition of IgA, C3 and OMHP antigens, glomerular changes (Mesangial hypercellularity and increase in mesangial matrix) after 20 weeks. The HP-PO group showed only mild deposition of IgA, and mild increase in mesangial matrix. These results suggest that OMHP antigens play a role in the glomerular deposition of IgA and C3 in C3H/HeN mice. This is the first use of OMHP antigens to establish an active model of IgAN.
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PMID:[Haemophilus parainfluenzae and IgA nephropathy]. 1051 4

Lipopolysaccharides (LPSs) were purified from Actinobacillus pleuropneumoniae serotype 2, Bordetella bronchiseptica and Haemophilus parasuis serotype 5, which were used for vaccine production in Japan, by the phenol-water procedure. In SDS-PAGE analysis, A. pleuropneumoniae LPS, as well as Escherichia coli LPS, demonstrated a typical ladder profile of a smooth-type LPS. On the other hand, B. bronchiseptica and H. parasuis LPSs lacked the ladder profiles. It was found that the biological activity of these LPSs was comparable to those of E. coli LPS in terms of activation of the clotting enzyme of Limulus amoebocyte lysate, mitogenic activity of mouse spleen cells, stimulation of TNF-alpha and nitric oxide production, but IL-6 production could hardly be observed in any LPS.
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PMID:Biological activities of lipopolysaccharides extracted from porcine vaccine strains. 1065 Oct 44

Two young children who suffered from thermal injuries to the epiglottis after swallowing corrosive agent and hot water respectively. Findings, clinically and radiologically, in both children were similar to acute infectious epiglottitis. Both recovered quickly with close observation and parenteral antibiotics. Although Haemophilus influenzae type b (Hib) is the major pathogen of epiglottitis, in areas with low incidence of Hib infection and high vaccination rates, non-infectious epiglottic swelling should be considered first.
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PMID:Non-infectious epiglottitis in children: two cases report. 1099 37


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