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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several bacterial isolated from human pharyngeal cultures specifically inhibited the growth of Legionella pneumophila. The inhibitory substance from two strains (Streptococcus species 1-3 and Staphylococcus saprophyticus KC) was isolated from a broth supernatant. The inhibitor was active against all strains of L. pneumophilia tested, including five strains of L. pneumophila serogroup 1 and one strain each of serogroups 2, 3, and 4. The substance did not inhibit growth of 18 fresh clinical and laboratory pathogens (12 general). The substance was dialyzable, was resistant to head and proteolysis, and did not precipitate with ammonium sulfate. Nicotinamide adenine dinucleotide, produced by several upper respiratory tract organisms, did not inhibit L. pneumophila, and L. pneumophila could not be isolated when Streptococcus species 1-3, S. saprophyticus KC, and L. pneumophila were cocultivated. These properties may in part explain the difficulty of isolation and may aid in the identification of L. pneumophila.
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PMID:Legionella pneumophila: growth inhibition by human pharyngeal flora. 744 Oct 2

A virulent strain of Legionella pneumophila serogroup 1, subgroup Pontiac, was grown in continuous culture at a constant growth rate under iron-replete and iron-limited conditions. Iron limitation was achieved by the removal of ferrous sulfate and hemin from the chemically defined medium. Residual contaminating iron, 0.45 microM, was sufficient to support iron-limited growth. Typical iron-replete cultures metabolized 3.3 microM iron. Serine provided the principal source of carbon and energy for both cultures, although iron-replete cultures also depleted a number of other amino acids. There was a 40% decrease in culture biomass under iron-restricted conditions. Iron limitation did not significantly affect carbohydrate metabolism, with the molar growth yield for carbon (Ycarbon) comparable for both cultures. However, under iron-limited conditions a sixfold increase in Yiron correlated with a significant decrease in the iron content of the biomass, as the culture utilized the available iron more efficiently. Highly pleomorphic iron-replete cultures became uniform cultures of short fine rods when adapted to iron-deficient conditions. In addition to the morphological and physiological changes, iron limitation had a critical effect on culture virulence. The virulence of this strain was significantly (P < 0.05) reduced when the culture was subjected to iron-limited conditions. This phenomenon was reversible, with a significant increase in culture virulence upon reversion to iron-replete conditions. When compared in an in vitro macrophage assay, the number of culturable avirulent iron-limited cells located intracellularly after infection was significantly lower than for the virulent replete and control cultures. These results further support the role of environmental parameters in regulating the virulence of L. pneumophila.
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PMID:Influence of iron-limited continuous culture on physiology and virulence of Legionella pneumophila. 759 Oct 51

Immunological cross-reactions among Legionella species were investigated with sonicated, proteinase K-digested cell lysates. The antigens separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were either analyzed for lipopolysaccharides (LPSs) by silver staining or transferred to nitrocellulose membranes for serological characterization with rabbit antibodies directed against Legionella pneumophila serogroups 1 and 5. When antiserum prepared against serogroup 5 was used to probe the LPSs from L. pneumophila serogroups 1 to 14, the antibodies recognized a common epitope harbored by all L. pneumophila serogroups but not by other Legionella species or by the gram-negative bacteria tested as controls. Hence, the serogroup 5 antiserum correctly identified all serogroups of L. pneumophila tested in the LPS immunoblot assay. Moreover, the silver-stained profiles of the isolated LPSs revealed characteristic patterns allowing the identification of the individual serogroups of L. pneumophila.
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PMID:Cross-reacting lipopolysaccharide antigens in Legionella pneumophila serogroups 1 to 14. 776 96

Legionella pneumophila is ingested by both human macrophages and amoebae, and it multiplies within similar endocytic compartments in both eukaryotic species. Inhibitors of eukaryotic protein synthesis, such as cycloheximide and emetine, had no effect on the uptake of L. pneumophila by macrophages but completely abolished ingestion by the amoeba Hartmannella vermiformis. Therefore, host cell protein synthesis is required for the bacterium to infect the amoeba but not human macrophages. To identify proteins expressed by H. vermiformis upon contact with L. pneumophila, we radiolabeled amoebal proteins after contact with bacteria in bacteriostatic concentrations of tetracycline to inhibit bacterial protein synthesis. We analyzed protein expression by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and found that 33 amoebal proteins were induced; 12 of these were not detected in resting amoebae. Eleven other amoebal proteins were repressed; four of them became undetectable. In contrast, no phenotypic changes were observed in H. vermiformis upon contact with Escherichia coli or heat-killed L. pneumophila. An isogenic, avirulent variant of L. pneumophila, incapable of infecting either macrophages or amoebae, induced a different pattern of protein expression upon contact with H. vermiformis. Our data showed that amoebae manifested a specific phenotypic response upon contact with virulent L. pneumophila. This phenotypic modulation may be necessary for uptake of the bacteria into an endocytic compartment that permits bacterial survival and multiplication.
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PMID:Protein expression by the protozoan Hartmannella vermiformis upon contact with its bacterial parasite Legionella pneumophila. 816 50

The role of the Legionella pneumophila protease in the pathogenesis of Legionnaires' disease is unclear. In this study, we assessed the effect of purified protease preparations on human recombinant interleukin-2 (IL-2), the IL-2 receptor, and several additional human T-cell surface proteins to determine whether protease contributes to the virulence of L. pneumophila by interfering with human T-cell activation and function. IL-2-induced proliferation of CTLL-2 cells was inhibited by coincubation with protease (10 to 100 U/ml). Protease at concentrations of > or = 10 U/ml cleaved human recombinant IL-2 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reaction mixtures containing 125I-labeled IL-2 and protease. Protease treatment of activated human T cells did not inhibit binding of a monoclonal antibody directed against the alpha subunit of the IL-2 receptor and did not interfere with binding of IL-2 to IL-2 receptors on the lymphocytes. Treatment of blood mononuclear cells or activated T cells with protease (50 U/ml) inhibited the binding of a monoclonal antibody directed against CD4. In contrast, protease treatment did not inhibit the binding of antibodies against CD3, CD8, class II major histocompatibility complex, and the transferrin receptor. Heat inactivation (65 degrees C for 20 min) of the protease or treatment with the metal chelator EDTA ablated the inhibitory effect of the protease. The ability of the protease to degrade IL-2 and cleave CD4 on human T cells suggests that protease may contribute to the pathogenesis of Legionnaires' disease by impeding T-cell activation and immune function.
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PMID:Legionella pneumophila protease inactivates interleukin-2 and cleaves CD4 on human T cells. 833 71

Ferric reductase enzymes requiring a reductant for maximal activity were purified from the cytoplasmic and periplasmic fractions of avirulent and virulent Legionella pneumophila. The cytoplasmic and periplasmic enzymes are inhibited by zinc sulfate, constitutive and active under aerobic or anaerobic conditions. However, the periplasmic and cytoplasmic reductases are two distinct enzymes as shown by their molecular weights, specific activities, reductant specificities and other characteristics. The molecular weights of the cytoplasmic and periplasmic ferric reductases are approximately 38 and 25 kDa, respectively. The periplasmic reductase (Km = 7.0 microM) has a greater specific activity and twice the affinity for ferric citrate as the cytoplasmic enzyme (Km = 15.3 microM). Glutathione serves as the optimum reductant for the periplasmic reductase, but is inactive for the cytoplasmic enzyme. In contrast, NADPH is the optimum reductant for the cytoplasmic enzyme. Ferric reductases of avirulent cells show a 2-fold increase in their activities when NADPH is used as a reductant in comparison with NADH. In contrast, ferric reductases from virulent cells demonstrated an equivalent activity with NADH or NADPH as reductants. With the exception of their response to NADPH, the ferric reductase at each respective location appears to be similar for avirulent and virulent cells.
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PMID:Ferric reductases of Legionella pneumophila. 835 4

Since many pathogenic bacteria manifest a coordinate regulation of gene expression in response to different environmental stimuli, we examined the phenotypic response of Legionella pneumophila to infection of macrophage-like U937 cells. Intracellular L. pneumophila was radiolabeled, and cell extracts were subjected to two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. At least 35 Legionella proteins were selectively induced during infection of macrophages, and one of these proteins was not detected in organisms grown in vitro. Expression of at least 32 proteins was selectively repressed during infection of macrophages, and 9 of these proteins were undetectable in intracellularly grown organisms. Thirteen of the macrophage-induced proteins were also induced by one or more of several stress conditions in vitro, and two of these proteins were the heat shock GroEL- and GroES-like proteins. Nineteen of the macrophage-repressed proteins were also repressed by one or more of the stress conditions in vitro. Our data showed that intracellular L. pneumophila manifested a phenotypic modulation and a global stress response to the intracellular environment of the macrophage. The data suggested that multiple regulons are involved in this modulation, which may contribute to the survival of L. pneumophila within alveolar macrophages.
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PMID:Phenotypic modulation by Legionella pneumophila upon infection of macrophages. 845 34

The results of a computer-assisted whole-cell protein sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of 291 isolates and 74 reference strains belonging to all known species of the genus Legionella revealed that the majority of the species of this genus can be adequately identified by this method. The type strain of Legionella bozemanii did not cluster with the other strains of this species, and the only strain of Legionella geestiana available clustered with the strains of Legionella feeleii. When we performed a numerical analysis by omitting certain portions of the pattern containing dense bands, all of the species could be distinguished. Our results also show that the type strains of Legionella nautarum and Legionella londiniensis deposited in the National Collection of Type Cultures do not correspond to the type strains deposited in the American Type Culture Collection. We used the results of a fatty acid and ubiquinone composition analysis to complement the SDS-PAGE results for several strains whose identities as determined by indirect immunofluorescence were doubtful. Computer-assisted SDS-PAGE of whole-cell proteins can be used in the classification of Legionella species and to identify and screen large numbers of isolates for further, in-depth taxonomic studies of smaller numbers of strains.
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PMID:Characterization of Legionella species by numerical analysis of whole-cell protein electrophoresis. 857 22

Legionella pneumophila 2064 was selectively radiolabelled in mouse L929 cells and human monocytes to identify proteins expressed early in the course of infection. Polypeptide profiles (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography) of adherent or intracellular bacteria indicated that a 60-kDa stress protein (Hsp60) was preferentially synthesized. Hsp60 synthesis was not induced by medium alone. The synthesis of many polypeptides, including OmpS (major outer membrane protein), diminished over the 1-h period postinfection. However, by 17 h postinfection OmpS and Hsp60 were the dominant proteins synthesized by 2064. To establish whether induction of Hsp60 was a correlate of virulence, an isogenic avirulent strain (2064M) of 2064 was isolated following selection on a nonpermissive medium. 2064M did not exhibit a stress response when adherent or intracellular in L929 cells or in human monocytes and failed to abrogate phagosome-lysosome fusion. When grown in vitro, 2064M exhibited no deficiencies in the heat shock response and its polypeptide profile resembled that of 2064. Immunogold electron microscopy was used to localize Hsp60 in L. pneumophila-infected L929 cells. There was an increase in the number of gold particles associated with phagosomes for phagosomes harboring single 2064 bacteria compared with those harboring 2064M. Moreover, by 1 h postinfection, a sixfold increase in the number of gold spheres associated with the membranes of phagosomes was observed for phagosomes harboring 2064 compared with those harboring 2064M. These studies indicate that virulent, but not NaCl-tolerant avirulent, strains of L. pneumophila respond to host-cell-associated environmental signals early in the course of infection. This response includes increased synthesis and possibly extracellular secretion of Hsp60 concomitant with repression of the expression of other genes, including ompS.
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PMID:Elevated levels of Legionella pneumophila stress protein Hsp60 early in infection of human monocytes and L929 cells correlate with virulence. 867 95

Levofloxacin is a fluoroquinolone antibiotic and is the optical S-(-) isomer of the racemic drug substance ofloxacin. It has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, as well as certain other pathogens such as Mycoplasma, Chlamydia, Legionella and Mycobacteria spp. Levofloxacin is significantly more active against bacterial pathogens than R-(+)-ofloxacin. Levofloxacin hemihydrate, the commercially formulated product, is 97.6% levofloxacin by weight. Levofloxacin pharmacokinetics are described by a linear 2-compartment open model with first-order elimination. Plasma concentrations in healthy volunteers reach a mean peak drug plasma concentration (Cmax) of approximately 2.8 and 5.2 mg/L within 1 to 2 hours after oral administration of levofloxacin 250 and 500mg tablets, respectively. The bioavailability of oral levofloxacin approaches 100% and is little affected by the administration with food. Oral absorption is very rapid and complete, with little difference in the serum concentration-time profiles following 500mg oral or intravenous (infused over 60 minutes) doses. Single oral doses of levofloxacin 50 to 1000mg produce a mean Cmax and area under the concentration-time curve (AUC) ranging from approximately 0.6 to 9.4 mg/L and 4.7 to 108 mg.h/L, respectively, both increasing linearly in a dose-proportional fashion. The pharmacokinetics of levofloxacin are similar during multiple-dose regimens to those following single doses. Levofloxacin is widely distributed throughout the body, with a mean volume of distribution of 1.1 L/kg, and penetrates well into most body tissues and fluids. Drug concentrations in tissues and fluids are generally greater than those observed in plasma, but penetration into the cerebrospinal fluid is relatively poor (concentrations approximately 16% of simultaneous plasma values). Levofloxacin is approximately 24 to 38% bound to serum plasma proteins (primarily albumin); serum protein binding is independent of serum drug concentrations. The plasma elimination half-life (t1/2 beta) ranges from 6 to 8 hours in individuals with normal renal function. Approximately 80% of levofloxacin is eliminated as unchanged drug in the urine through glomerular filtration and tubular secretion; minimal metabolism occurs with the formation of no metabolites possessing relevant pharmacological activity. Renal clearance and total body clearance are highly correlated with creatinine clearance (CLCR), and dosage adjustments are required in patients with significant renal dysfunction. Levofloxacin pharmacokinetics are not appreciably affected by age, gender or race when differences in renal function, and body mass and composition are taken into account. Important drug interactions exist with aluminium- and magnesium-containing antacids and ferrous sulfate, as with other fluoroquinolones, resulting in significantly decreased levofloxacin absorption when administered concurrently. These agents should be administered at least 2 hours before or after levofloxacin administration. Cimetidine and probenecid decrease levofloxacin renal clearance and increase t1/2 beta; the magnitudes of these interactions are not clinically significant. Levofloxacin appears to have only minor potential for significantly altering the pharmacokinetics of theophylline, warfarin, zidovudine, ranitidine, digoxin or cyclosporin; however, patients receiving these drugs concurrently should be monitored closely for signs of enhanced pharmacological effect or toxicity. Levofloxacin pharmacokinetics are not significantly altered by sucralfate when administration of these drugs is separated by at least 2 hours.
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PMID:The clinical pharmacokinetics of levofloxacin. 906 26


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