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)

Pathogenic Haemophilus influenzae, Neisseria spp. (Neisseria gonorrhoeae and N. meningitidis), Serratia marcescens, and other gram-negative bacteria utilize a periplasm-to-cytosol FbpABC iron transporter. In this study, we investigated the H. influenzae FbpABC transporter in a siderophore-deficient Escherichia coli background to assess biochemical aspects of FbpABC transporter function. Using a radiolabeled Fe3+ transport assay, we established an apparent Km=0.9 microM and Vmax=1.8 pmol/10(7)cells/min for FbpABC-mediated transport. Complementation experiments showed that hFbpABC is dependent on the FbpA binding protein for transport. The ATPase inhibitor sodium orthovanadate demonstrated dose-dependent inhibition of FbpABC transport, while the protonmotive-force-inhibitor carbonyl cyanide m-chlorophenyl hydrazone had no effect. Metal competition experiments demonstrated that the transporter has high specificity for Fe3+ and selectivity for trivalent metals, including Ga3+ and Al3+, over divalent metals. Metal sensitivity experiments showed that several divalent metals, including copper, nickel, and zinc, exhibited general toxicity towards E. coli. Significantly, gallium-induced toxicity was specific only to E. coli expressing FbpABC. A single-amino-acid mutation in the gene encoding the periplasmic binding protein, FbpA(Y196I), resulted in a greatly diminished iron binding affinity Kd=5.2 x 10(-4) M(-1), approximately 14 orders of magnitude weaker than that of the wild-type protein. Surprisingly, the mutant transporter [FbpA(Y196I)BC] exhibited substantial transport activity, approximately 35% of wild-type transport, with Km=1.2 microM and Vmax=0.5 pmol/10(7)cells/min. We conclude that the FbpABC complexes possess basic characteristics representative of the family of bacterial binding protein-dependent ABC transporters. However, the specificity and high-affinity binding characteristics suggest that the FbpABC transporters function as specialized transporters satisfying the strict chemical requirements of ferric iron (Fe3+) binding and membrane transport.
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PMID:The hFbpABC transporter from Haemophilus influenzae functions as a binding-protein-dependent ABC transporter with high specificity and affinity for ferric iron. 1534 92

IscU is a highly conserved protein that serves as the scaffold for IscS-mediated assembly of iron-sulfur ([Fe-S]) clusters. We report the NMR solution structure of monomeric Haemophilus influenzae IscU with zinc bound at the [Fe-S] cluster assembly site. The compact core of the globular structure has an alpha-beta sandwich architecture with a three-stranded antiparallel beta-sheet and four alpha-helices. A nascent helix is located N-terminal to the core structure. The zinc is ligated by three cysteine residues and one histidine residue that are located in and near conformationally dynamic loops at one end of the IscU structure. Removal of the zinc metal by chelation results in widespread loss of structure in the apo form. The zinc-bound IscU may be a good model for iron-loaded IscU and may demonstrate structural features found in the [Fe-S] cluster bound form. Structural and functional similarities, genomic context in operons containing other homologous genes, and distributions of conserved surface residues support the hypothesis that IscU protein domains are homologous (i.e. derived from a common ancestor) with the SufE/YgdK family of [Fe-S] cluster assembly proteins.
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PMID:Solution NMR structure of the iron-sulfur cluster assembly protein U (IscU) with zinc bound at the active site. 1552 5

Although most cases of acute rhinosinusitis are caused by viruses, acute bacterial rhinosinusitis is a fairly common complication. Even though most patients with acute rhinosinusitis recover promptly without it, antibiotic therapy should be considered in patients with prolonged or more severe symptoms. To avoid the emergence and spread of antibiotic-resistant bacteria, narrow-spectrum antibiotics such as amoxicillin should be used for 10 to 14 days. In patients with mild disease who have beta-lactam allergy, trimethoprim/sulfamethoxazole or doxycycline are options. Second-line antibiotics should be considered if the patient has moderate disease, recent antibiotic use (past six weeks), or no response to treatment within 72 hours. Amoxicillin-clavulanate potassium and fluoroquinolones have the best coverage for Haemophilus influenzae and Streptococcus pneumoniae. In patients with beta-lactam hypersensitivity who have moderate disease, a fluoroquinolone should be prescribed. The evidence supporting the use of ancillary treatments is limited. Decongestants often are recommended, and there is some evidence to support their use, although topical decongestants should not be used for more than three days to avoid rebound congestion. Topical ipratropium and the sedating antihistamines have anticholinergic effects that maybe beneficial, but there are no clinical studies supporting this possibility. Nasal irrigation with hypertonic and normal saline has been beneficial in chronic sinusitis and has no serious adverse effects. Nasal corticosteroids also may be beneficial in treating chronic sinusitis. Mist, zinc salt lozenges, echinacea extract, and vitamin C have no proven benefit in the treatment of acute bacterial rhinosinusitis.
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PMID:Acute bacterial rhinosinusitis in adults: part II. Treatment. 1630 28

Under-five mortality varies widely between countries, ranging from four to over 300 deaths/1000 live births. The World Summit for Children established the aim of a two-thirds reduction in worldwide child mortality by 2015. Progress toward this goal during 1990-2000 was variable between world regions. In 2000, 70% of the 1.89 million deaths of children under the age of 5 years due to acute respiratory infections occurred in developing countries. Among Latin American countries, Chile and Uruguay had the lowest percentage of deaths (5-10%), while Bolivia, Peru and Guyana had the highest (15-20%). Mortality rates due to lower respiratory infections have declined in most countries, increased in some and remained unacceptably high in others. To reach the 2015 goal of reducing mortality in the under-fives, effective interventions, such as breastfeeding and complementary feeding, Haemophilus influenzae type B vaccine, zinc supplementation and the use of antibiotics to treat pneumonia need to be implemented in all Latin American countries.
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PMID:The burden of pneumonia in children in Latin America. 1591 52

Pneumonia results in two million deaths each year among children worldwide (20% of all child deaths), 70% of them in Africa and South-east Asia. Most countries in Africa and Asia record 2-10 times more children with pneumonia (7-40/100 annually) than in the USA. Apart from resource constraints and an overburdened health system, there is lack of uniformity in defining pneumonia. Most nations employ a WHO standard case management protocol using age-specific cut-offs for increased respiratory rates and chest in-drawing for a clinical definition of pneumonia. The limited data available on the causative organisms have identified Streptococcus pneumoniae, Haemophilus influenzae and viruses such as respiratory syncytial virus (RSV), influenza, para influenza and adenoviruses as the major pathogens. Measles infection increases pneumonia morbidity and mortality. Low birth weight, under-nutrition, hypovitaminosis A, zinc deficiency, lack of breastfeeding, air pollution (including environmental tobacco smoke) and over-crowding increase the risk for pneumonias in children. Standard case management protocols used for acute respiratory infections (ARIs) in these countries have brought down the disease burden but an improvement in the diagnostic algorithm is needed to appropriately recognise those with associated wheeze. Research is needed to find effective and affordable preventive strategies.
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PMID:The burden of pneumonia in children: an Asian perspective. 1591 53

SecB is a molecular chaperone that functions in bacterial post-translational protein translocation pathway. It maintains newly synthesized precursor polypeptide chains in a translocation-competent state and guides them to the translocon via its high-affinity binding to the ligand as well as to the membrane-embedded ATPase SecA. Recent advances in elucidating the structures of SecB have enabled the examination of protein function in the structural context. Structures of SecB from both Haemophilus influenzae and Escherichia coli support the early two-subsite polypeptide-binding model. In addition, the detailed molecular interaction between SecB and SecA was revealed by a structure of SecB in complex with the C-terminal zinc-containing domain of SecA. These observations explain the dual role of SecB plays in the translocation pathway, as a molecular chaperone and a specific targeting factor. A model of SecB-SecA complex suggests that the binding of SecA to SecB changes the conformation of the polypeptide binding sites in the chaperone, enabling transfer of precursor polypeptides from SecB to SecA. Recent studies also show the presence of a second zinc-independent SecB binding site in SecA and the new interaction might contribute to the function of SecB.
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PMID:The structural view of bacterial translocation-specific chaperone SecB: implications for function. 1619 24

The structures of beta class carbonic anhydrases (beta-CAs) determined so far fall into two distinct subclasses based on the observed coordination of the catalytic zinc (Zn2+) ion. The subclass of beta-CAs that coordinate Zn2+ tetrahedrally with four protein-derived ligands is represented by the structures of orthologues from Porphyridium purpureum, Escherichia coli, and Mycobacterium tuberculosis. Here we present the structure of an additional member of that subclass, that from Haemophilus influenzae, as well as detailed kinetic analysis, revealing the correspondence between structural classification and kinetic profile for this subclass. In addition, we identify a unique, noncatalytic binding mode for the substrate bicarbonate that occurs in both the H. influenzae and E. coli enzymes. The kinetic and structural analysis indicates that binding of bicarbonate in this site of the enzyme may modulate its activity by influencing a pH-dependent, cooperative transition between active and inactive forms. We hypothesize that the two structural subclasses of beta-CAs may provide models for the proposed active and inactive forms of the H. influenzae and E. coli enzymes.
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PMID:Identification of a novel noncatalytic bicarbonate binding site in eubacterial beta-carbonic anhydrase. 1658 70

An essential role for zinc in development of the fetal immune system has been documented. However, the effect of antenatal zinc supplementation on infants' postnatal immune response to vaccinations is unknown. The objective of this study was to evaluate the effect of zinc supplementation during pregnancy on immune response to the Bacillus Calmette-Guerin (BCG) vaccine and the Haemophilus influenzae type b (Hib) component of the combined diphtheria, tetanus toxoid and pertussis (DTP)-Haemophilus influenzae type-b (Hib)- conjugate vaccine in poor Bangladeshi infants. We immunized 405 infants whose mothers were supplemented daily with 30 mg elemental zinc or placebo beginning at 12-16 weeks gestation with the standard BCG vaccine at birth. A subcohort of 203 infants were in addition immunized at 1-month intervals with three doses of DTP-Hib vaccine starting at 9 weeks of age. The delayed hypersensitivity (PPD) skin test was performed in 345 infants at 24 weeks of age. Hib polysaccharide (PRP) antibodies were assessed for 91 infants at 4 and 24 weeks of age. In infants born with low birth weight (LBW) a lower proportion of negative responses to PPD skin test were observed in the zinc (66.2%) compared to placebo (78.5%) group (p = 0.07). No differences were observed in normal birth weight infants. There were no differences in proportion of infants above the protective thresholds for anti-PRP antibodies between zinc (81%) and placebo (89%) group. Geometric mean PRP antibody titres at 4 and 24 weeks of age were not different between groups. Zinc supplementation during pregnancy did not enhance immune response to Hib-conjugate vaccine but there was a suggestion of improved delayed hypersensitivity immune responses to BCG-vaccine in Bangladeshi LBW infants.
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PMID:The effect of zinc supplementation during pregnancy on immune response to Hib and BCG vaccines in Bangladesh. 1662 58

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin (HL(1) and HL(2), respectively) were synthesized and characterized, being the crystal structures of HL(1), HL(2) and [Ni(L(1))(2)].2CHCl(3) elucidated by X-ray diffraction techniques. The in vitro antimicrobial activity of all these compounds was tested against several bacteria and fungi. HL(1)and its complexes exhibited a strong inhibition of the growth of Haemophilus influenzae (MIC 0.15-1.50microg/mL) and good antibacterial properties towards Bacillus subtilis (MIC 3-25microg/mL). The minimal inhibitory concentration (MIC) was defined as the lowest concentration of compound inhibiting the growth of each strain. The antibacterial effectiveness was confirmed against a number of Gram positive bacteria, including methicillin-resistant Staphylococcus aureus. Yeasts and moulds showed a low susceptibility, except the dermatophyte mould Epidermophyton floccosum that is inhibited at concentrations ranging from 6 to 50microg/mL. In general, the antimicrobial activity of the thiophene derivatives was greater than that of the isonicotinic analogues.
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PMID:Complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin. A study of their antimicrobial activity. 1707 Sep 19

Four epidemiologically unrelated Haemophilus influenzae serotype a (Hia) strains from patients in Quebec, Canada, were characterized and found to represent 3 distinct groups. One isolate, found to be biotype I and sequence type (ST)-62 by multilocus sequence typing, was shown to possess the copper- and zinc-containing superoxide dismutase gene, sodC, and was suspected to belong to clonal division II. The other 3 isolates were classified as clonal division I based on the absence of the sodC gene. Among the 3 sodC-negative Hia strains, 2 were biotype II and had related STs (ST-23 and ST-403) and highly similar DNA fingerprints, similar to a group of previously described Hia isolates causing invasive disease in Manitoba, Canada. The remaining sodC-negative strain belonged to biotype I and ST-4 and shared no common allele with ST-23, ST-403, or ST-62. This isolate also possessed the IS1016-bexA partial deletion, which is often associated with increased virulence. Despite the small number of isolates used in this study, our finding of 3 distinct groups shows the existence of a potential genetic diversity not previously described for Hia. Whether this genetic diversity is related to the severity and epidemiology of Hia disease requires further studies.
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PMID:Molecular characterization of four Haemophilus influenzae serotype a strains isolated from patients in Quebec, Canada. 1802 12


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