UMLS:C0014118 - FACTA Search

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Query: UMLS:C0014118 (endocarditis)
15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-695,256 is a synthetic carbapenem beta-lactam antibiotic that binds with a high degree of affinity to penicillin-binding protein (PBP) PBP 2a, the protein that mediates staphylococcal resistance to methicillin. The concentration of L-695,256 that inhibited binding of radiolabeled [3H]penicillin to PBP 2a by 50% was 1.2 micrograms/ml, whereas they were 14 and 68 micrograms/ml for penicillin and imipenem, respectively. Cell wall synthesis, determined by incorporation of [14C]N-acetylglucosamine into whole cells, was inhibited by 50% at concentrations of 1.3, 26, and 132 micrograms/ml for L-695,256, penicillin, and imipenem, respectively, for the methicillin-resistant strain COL. Growth of cells of each of two homogeneously resistant strains, COL and 76, was completely inhibited by 4 micrograms of L-695,256 per ml, whereas growth was inhibited by 100 micrograms or more of penicillin or imipenem per ml. The efficacies of L-695,256 (10 mg/kg given three times daily [t.i.d.]), imipenem (37.5 mg/kg t.i.d.), penicillin (300,000 units/kg t.i.d.), and vancomycin (25 mg/kg given twice daily) were compared in the rabbit model of aortic valve endocarditis established with these homogeneous strains. After 4 days of treatment, mean bacterial densities in aortic valve vegetations were reduced by 4.0 to 5.8 log10 CFU/g for L-695,256, 1.0 to 1.8 log10 CFU/g for imipenem, -1.1 to 3.9 log10 CFU/g for penicillin, and 1.1 to 3.0 log10 CFU/g for vancomycin in comparison to the densities of controls. Compounds such as L-695,256 that are bound by PBP 2a with a high degree of affinity are likely to be extremely effective in the treatment of infections caused by methicillin-resistant staphylococci.
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PMID:In vitro and in vivo antistaphylococcal activities of L-695,256, a carbapenem with high affinity for the penicillin-binding protein PBP 2a. 772 16

The expression of sialy-Lewis(x) (sLe(x); Neu5Ac alpha 2-3 Gal beta 1-4) (Fuc alpha 1-3) GlcNAc-R) on oral bacteria producing infective endocarditis was determined by a whole-cell enzyme linked immunosorbent assay and an immunoelectron microscopy using the well-characterized anti-sLe(x) monoclonal antibody SNH-3 (mAb SNH-3; IgM class). mAb SNH-3 reacted strongly with whole cells of oral bacteria: Streptococcus sanguis, Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Streptococcus intermedius, Streptococcus constellatus, Streptococcus anginosus, Streptococcus pyogenes, Actinobacillus actinomycetemcomitans, Eikenella corrodens and Porphyromonas gingivalis. The negatively stained immuno-electron micrograph of Streptococcus pyogenes showed many reactive gold particles on the cell surface. Our findings demonstrated the existence of immunologic mimicry between the sLe(x) oligosaccharide and cell surface antigens of many species associated with infective endocarditis. We propose the hypothesis that if these bacteria escape their normal habitats, the surface components that mimic the sLe(x) oligosaccharide might bind to host antigens of the selectin family which could promote binding to endothelial cells and, consequently, initiation of the events leading to infective endocarditis.
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PMID:Cross-reactivity between human sialyl Lewis(x) oligosaccharide and common causative oral bacteria of infective endocarditis. 858 66

Nine strains of Streptococcus oralis, isolated from blood cultures of patients with infective endocarditis or from the oral cavity as part of the normal flora, were examined for their ability to elaborate sialidase (neuraminidase) and N-acetylglucosaminidase, enzymes which are involved in the degradation of glycoproteins. Both glycosidases were induced when bacteria were grown in a minimal medium supplemented with porcine gastric mucin, a model glycoprotein, and repressed when growth occurred in the presence of glucose. Cell-free extracts mucin-grown cultures expressed elevated levels of N-acetylneuraminate pyruvate-lyase (the first intracellular enzyme in the pathway of N-acetylneuraminate catabolism), N-acetylglucosamine (glcNAc)-6-phosphate deacetylase and glucosamine-6-phosphate deaminase (enzymes involved in the intracellular catabolism of GlcNAc 6-phosphate); activity of each of these intracellular enzymes was markedly repressed when bacteria were grown in media supplemented with alpha 1-acid glycoprotein, a major component of human plasma. Cells from these cultures expressed high levels of sialidase, N-acetylglucosaminidase, and the intracellular enzymes involved in the catabolism of N-acetyl-sugars released by action of these glycosidases. High-resolution 1H-NMR spectroscopy of spent culture supernatants revealed that sialic acid and GlcNAc residues of the molecularly mobile oligosaccharide side-chains of alpha 1-acid glycoprotein had been hydrolysed and the released sugars internalized by the bacteria. These data indicate that S. oralis has the ability to hydrolyse constituents of oligosaccharide side-chains of host-derived glycoproteins and to utilize simultaneously these released carbohydrates. The biochemical characteristics induced by the growth of S. oralis on glycoproteins may play a role in the survival and persistence of these bacteria at the infection site in vivo.
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PMID:Metabolism of glycoprotein-derived sialic acid and N-acetylglucosamine by Streptococcus oralis. 870 62

The importance of viridans streptococci as agents of serious extra-oral diseases, including endocarditis, is now recognized. We have tested the hypothesis that the ability to utilize sialic acid as a nutrient source may play a role in the proliferation of these organisms. The type strains of the 15 presently recognized species of viridans streptococci and two clinical isolates-S. oralis (AR3), isolated from a patient with infective endocarditis, and S. intermedius (UNS35), a brain abscess isolate-were studied for their ability to utilize sialic acid. Only S. oralis, S. sanguis, S. gordonii, S. mitis ("oralis group") S. intermedius, S. anginosus, S. constellatus ("milleri group"), and S. defectivus ("nutritionally variant group") were able to use sialic acid (N-acetylneuraminic acid) efficiently as a sole carbon source. Formate, acetate, and ethanol were produced as the major metabolic end-products of sialic acid metabolism, while corresponding glucose-grown cultures produced lactate as the major metabolic end-product. Utilization of sialic acid was independent of the production of sialidase. Cell-free extracts of sialic acid-grown cultures expressed elevated levels of N-acetylneuraminate pyruvate-lyase (NPL; the first enzyme in the intracellular catabolism of sialic acid) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P) deacetylase and glucosamine-6-phosphate (GlcN-6-P) deaminase (enzymes involved in the intracellular catabolism of N-acetylglucosamine). These activities were repressed by growth in the presence of glucose. The intracellular fate of sialic acid, after cleavage by NPL into N-acetylmannosamine (ManNAc) and pyruvate, is uncertain, but the elevated levels of GlcNAc-6-P deacetylase and GlcN-6-P deaminase in sialic acid-grown cells suggest that phosphorylation and isomerization are possible steps in the metabolism of ManNAc to generate an intermediate common to the pathway of N-acetylglucosamine metabolism. The species of viridans streptococci that have the ability to utilize sialic acid are those most commonly associated with extra-oral diseases, and this ability is likely to play a role in the persistence and survival of these infecting organisms in vivo.
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PMID:Utilization of sialic acid by viridans streptococci. 890 24

Streptococcus oralis has emerged as one of the most important organisms of the viridans streptococcus group in terms of infections and is recognised as an agent of infective endocarditis and, in immunocompromised patients, septicaemia. The mechanisms by which this organism proliferates in vivo are unknown. However, host-derived sialic acids -- including N-acetylneuraminic acid (NeuNAc) which is present in serum and cell-associated glycoproteins -- are a potential source of fermentable carbohydrate for bacterial proliferation, especially for sialidase-producing bacteria, including S. oralis. To further elucidate the role of NeuNAc in supporting growth, this study determined the ability of S. oralis strain AR3 (isolated from a patient with infective endocarditis) to transport NeuNAc and characterised the transport system. The transport of [14C]-labelled NeuNAc into S. oralis was monitored and this transport system was induced by growth of the bacteria in the presence of the N-acetylated sugars NeuNAc, N-acetylglucosamine and N-acetylmannosamine. The transport system followed typical Michaelis-Menten kinetics, with a Km of 21.0 microM and a Vmax of 2.65 nmoles of NeuNAc transported/min/mg of dry cell mass. NeuNAc transport was inhibited by the presence of exogenous N-glycolylneuraminic acid, a related sialic acid. Chlorhexidine, NaF and 2,4-dinitrophenol were potent inhibitors of the transport system, suggesting that the uptake of NeuNAc occurs via a proton motive force-dependent permease system. This is the first report of the mechanism by which NeuNAc transport occurs in pathogenic streptococci. This transport process may have relevance to the acquisition of a source of fermentable carbohydrate and thus bacterial proliferation in vivo.
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PMID:N-acetylneuraminic acid transport by Streptococcus oralis strain AR3. 1050 80

The binding of bacteria and platelets may play a central role in the pathogenesis of infective endocarditis. Platelet binding by Streptococcus gordonii strain M99 is predominantly mediated by the 286-kDa cell wall-anchored protein GspB. This unusually large protein lacks a typical amino-terminal signal peptide and is translocated from the cytoplasm via a dedicated transport system. A 14-kb segment just downstream of gspB encodes SecA2 and SecY2, two components of the GspB-specific transport system. The downstream segment also encodes several putative glycosyl transferases that may be responsible for the posttranslational modification of GspB. In this study, we compared the abilities of M99 and two GspB(-) mutant strains to bind various lectins. GspB was found to have affinity for lectins that bind N-acetylglucosamine. We also examined variant forms of GspB that lack a carboxy-terminal cell wall-anchoring domain and thus are free of covalent linkage to cell wall peptidoglycan. Like native GspB, these truncated proteins appear to be heavily glycosylated, as evidenced by migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass >100 kDa in excess of the predicted mass, negligible staining with conventional protein stains, and reactivity with hydrazide following periodate oxidation. Furthermore, analysis of the carbohydrate associated with the GspB variants by high-pH anion-exchange chromatography revealed the presence of approximately 70 to 100 monosaccharide residues per GspB polypeptide (primarily N-acetylglucosamine and glucose). Analysis of GspB in protoplasts of secA2 or secY2 mutant strains, which do not export GspB, indicates that GspB is glycosylated in the cytoplasm of these strains. The combined data suggest that the native GspB is a glycoprotein and that it may be glycosylated prior to export.
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PMID:The Streptococcus gordonii platelet binding protein GspB undergoes glycosylation independently of export. 1472 88

Staphylococcus lugdunensis is a pathogen of heightened virulence that causes infections resembling those caused by Staphylococcus aureus rather than those caused by its coagulase-negative staphylococcal counterparts. Many types of S. lugdunensis infection, including native valve endocarditis, prosthetic joint infection, and intravascular catheter-related infection, are associated with biofilm etiology. Poly-N-acetylglucosamine (PNAG), a polysaccharide synthesized by products of the icaADBC locus, is a common mechanism of intercellular adhesion in staphylococcal biofilms. Here we report the characterization of ica homologues and the in vitro biofilm formation properties of a collection of S. lugdunensis clinical isolates. Isolates formed biofilms in microtiter wells to various degrees. Biofilm formation by most isolates was enhanced with glucose but diminished by sodium chloride or ethanol. icaADBC homologues were found in all S. lugdunensis isolates tested, although the locus organization differed substantially from that of other staphylococcal ica loci. icaR was not detected in S. lugdunensis, but a novel open reading frame with putative glycosyl hydrolase function is located upstream of the ica locus. icaADBC sequence heterogeneity did not explain the variability in biofilm formation among isolates. PNAG was not detected in S. lugdunensis extracts by immunoblotting with an anti-deacetylated PNAG antibody or wheat germ agglutinin. Confocal microscopy with fluorescently labeled wheat germ agglutinin showed a paucity of PNAG in S. lugdunensis biofilms, but abundant extracellular protein was visualized with SYPRO Ruby staining. Biofilms were resistant to detachment by dispersin B and sodium metaperiodate but were susceptible to detachment by proteases. Despite the genetic presence of icaADBC homologues in S. lugdunensis isolates, PNAG is not a major component of the extracellular matrix of in vitro biofilms formed by this species. Our data suggest that the S. lugdunensis biofilm matrix contains proteinaceous factors.
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PMID:Poly-N-acetylglucosamine is not a major component of the extracellular matrix in biofilms formed by icaADBC-positive Staphylococcus lugdunensis isolates. 1763 64

Phosphoglucosamine mutase (EC 5.4.2.10) catalyzes the interconversion of glucosamine-6-phosphate into glucosamine-1-phosphate, an essential step in the biosynthetic pathway leading to the formation of peptidoglycan precursor uridine 5'-diphospho-N-acetylglucosamine. The gene (glmM) of Escherichia coli encoding the enzyme has been identified previously. We have now identified a glmM homolog in Streptococcus gordonii, an early colonizer on the human tooth and an important cause of infective endocarditis, and have confirmed that the gene encodes phosphoglucosamine mutase by assaying the enzymatic activity of the recombinant GlmM protein. Insertional glmM mutant of S. gordonii did not produce GlmM, and had a growth rate that was approximately half that of the wild type. Morphological analyses clearly indicated that the glmM mutation causes marked elongation of the streptococcal chains, enlargement of bacterial cells, and increased roughness of the bacterial cell surface. Furthermore, the glmM mutation reduces biofilm formation and increases sensitivity to penicillins relative to wild type. All of these phenotypic changes were also observed in a glmM deletion mutant, and were restored by the complementation with plasmid-borne glmM. These results suggest that, in S. gordonii, mutations in glmM appear to influence bacterial cell growth and morphology, biofilm formation, and sensitivity to penicillins.
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PMID:Identification of the Streptococcus gordonii glmM gene encoding phosphoglucosamine mutase and its role in bacterial cell morphology, biofilm formation, and sensitivity to antibiotics. 1846 86

Staphylococcus epidermidis is one of the most common causes of infections of prosthetic heart valves (prosthetic valve endocarditis [PVE]) and an increasingly common cause of infections of native heart valves (native valve endocarditis [NVE]). While S. epidermidis typically causes indolent infections of prosthetic devices, including prosthetic valves and intravascular catheters, S. epidermidis NVE is a virulent infection associated with valve destruction and high mortality. In order to see if the differences in the course of infection were due to characteristics of the infecting organisms, we examined 31 S. epidermidis NVE and 65 PVE isolates, as well as 21 isolates from blood cultures (representing bloodstream infections [BSI]) and 28 isolates from nasal specimens or cultures considered to indicate skin carriage. Multilocus sequence typing showed both NVE and PVE isolates to have more unique sequence types (types not shared by the other groups; 74 and 71%, respectively) than either BSI isolates (10%) or skin isolates (42%). Thirty NVE, 16 PVE, and a total of 9 of the nasal, skin, and BSI isolates were tested for virulence in Caenorhabditis elegans. Twenty-one (70%) of the 30 NVE isolates killed at least 50% of the worms by day 5, compared to 1 (6%) of 16 PVE isolates and 1 (11%) of 9 nasal, skin, or BSI isolates. In addition, the C. elegans survival rate as assessed by log rank analyses of Kaplan-Meier survival curves was significantly lower for NVE isolates than for each other group of isolates (P < 0.0001). There was no correlation between the production of poly-beta(1-6)-N-acetylglucosamine exopolysaccharide and virulence in worms. This study is the first analysis suggesting that S. epidermidis isolates from patients with NVE constitute a more virulent subset within this species.
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PMID:Analysis of the genotype and virulence of Staphylococcus epidermidis isolates from patients with infective endocarditis. 1879 84

Phosphoglucosamine mutase (GlmM; EC 5.4.2.10) catalyzes the interconversion of glucosamine-6-phosphate to glucosamine-1-phosphate, an essential step in the biosynthetic pathway leading to the formation of the peptidoglycan precursor uridine 5'-diphospho-N-acetylglucosamine. We have recently identified the gene (glmM) encoding the enzyme of Streptococcus gordonii, an early colonizer on the human tooth and an important cause of infective endocarditis, and indicated that the glmM mutation in S. gordonii appears to influence bacterial cell growth, morphology, and sensitivity to penicillins. In the present study, we assessed whether the glmM mutation also affects escape from polymorphonuclear leukocyte (PMN)-dependent killing. Although no differences in attachment to human PMNs were observed between the glmM mutant and the wild-type S. gordonii, the glmM mutation resulted in increased sensitivity to PMN-dependent killing. Compared with the wild type, the glmM mutant induced increased superoxide anion production and lysozyme release by PMNs. Moreover, the glmM mutant is more sensitive to lysozyme, indicating that the GlmM may be required for synthesis of firm peptidoglycans for resistance to bacterial cell lysis. These findings suggest that the GlmM contributes to the resistance of S. gordonii to PMN-dependent killing. Enzymes such as GlmM could be novel drug targets for this organism.
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PMID:Contribution of phosphoglucosamine mutase to the resistance of Streptococcus gordonii DL1 to polymorphonuclear leukocyte killing. 1955 11

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