Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There have been reported outbreaks of Legionnaires' disease at hospitals and industrial facilities, which prompted the development of various preventive measures. For example, Ford has been developing and implementing such a measure at its facilities worldwide to provide technical guidance for controlling Legionella in water systems. One of the key issues for implementing the measure is the selection of a disinfectant(s) and optimum conditions for its use. Therefore, available publications on various disinfectants and disinfection processes used for the inactivation of Legionella bacteria were reviewed. Two disinfection methods were reviewed: chemical and thermal. For chemical methods, disinfectants used were metal ions (copper and silver), oxidizing agents (halogen containing compounds [chlorine, bromine, iodine, chlorine dioxide, chloramines, and halogenated hydantoins], ozone, and hydrogen peroxide), non-oxidizing agents (heterocyclic ketones, guanidines, thiocarbamates, aldehydes, amines, thiocyanates, organo-tin compounds, halogenated amides, and halogenated glycols), and UV light. In general, oxidizing disinfectants were found to be more effective than non-oxidizing ones. Among oxidizing agents, chlorine is known to be effective and widely used. Among non-oxidizing agents, 2,2-dibromo-3-nitropropionamide appears to be the most effective followed by glutaraldehyde. Isothiazolin (known as Kathon), polyhexamethylene biguanide, and 2-bromo-2-nitropropionamide (known as Bronopol) were found to be less effective than glutaraldehyde. Thermal disinfection is effective at > 60 degrees C (140 degrees F).
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PMID:Literature review--efficacy of various disinfectants against Legionella in water systems. 1241 46

Legionella pneumophila, a parasite of aquatic amoebae and pathogen of pulmonary macrophages, replicates intracellularly, utilizing a type IV secretion system to subvert the trafficking of Legionella-containing phagosomes. Defense against host-derived reactive oxygen species has been proposed as critical for intracellular replication. Virulence traits of null mutants in katA and katB, encoding the two Legionella catalase-peroxidases, were analyzed to evaluate the hypothesis that L. pneumophila must decompose hydrogen peroxide to establish a replication niche in macrophages. Phagosomes containing katA or katB mutant Legionella colocalize with LAMP-1, a late endosomal-lysosomal marker, at twice the frequency of those of wild-type strain JR32 and show a decreased frequency of bacterial replication, in similarity to phenotypes of mutants with mutations in dotA and dotB, encoding components of the Type IV secretion system. Quantitative similarity of the katA/B phenotypes indicates that each contributes to virulence traits largely independently of intracellular compartmentalization (KatA in the periplasm and KatB in the cytosol). These data support a model in which KatA and KatB maintain a critically low level of H(2)O(2) compatible with proper phagosome trafficking mediated by the type IV secretion apparatus. During these studies, we observed that dotA and dotB mutations in wild-type strain Lp02 had no effect on intracellular multiplication in the amoeba Acanthamoeba castellanii, indicating that certain dotA/B functions in Lp02 are dispensable in that experimental model. We also observed that wild-type JR32, unlike Lp02, shows minimal contact-dependent cytotoxicity, suggesting that cytotoxicity of JR32 is not a prerequisite for formation of replication-competent Legionella phagosomes in macrophages.
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PMID:Legionella pneumophila catalase-peroxidases are required for proper trafficking and growth in primary macrophages. 1287 32

Legionella pneumophila, the causative agent of Legionnaires' disease, expresses a type IVB secretion apparatus that translocates bacterial proteins into amoeba and macrophage hosts. When stationary-phase cultures are used to infect hosts, the type IVB apparatus encoded by the icm/dot genes is required for entry, delay of phagosome-lysosome fusion, and intracellular multiplication within host cells. Null mutants with mutations in icm/dot genes are defective in these phenotypes. Here a new model is described in which hosts are infected with stationary-phase cultures that have been incubated overnight in pH 6.5 buffer. This model is called Ers treatment because it enhances the resistance to acid, hydrogen peroxide, and antibiotic stress beyond that of stationary-phase cultures. Following Ers treatment entry into amoeba and macrophage hosts does not require dotA, which is essential for Legionella virulence phenotypes when hosts are infected with stationary-phase cultures, dotB, icmF, icmV, or icmX. Defective host entry is also suppressed for null mutants with mutations in the KatA and KatB catalase-peroxidase enzymes, which are required for proper intracellular growth in amoeba and macrophage hosts. Ers treatment-induced suppression of defective entry is not associated with increased bacterial adhesion to host cells or with morphological changes in the bacterial envelope but is dependent on protein expression during Ers treatment. By using proteomic analysis, Ers treatment was shown to induce a protein predicted to contain eight tetratricopeptide repeats, a motif previously implicated in enhanced entry of L. pneumophila. Characterization of Ers treatment-dependent changes in expression is proposed as an avenue for identifying icm/dot-independent factors that function in the entry of Legionella into amoeba and macrophage hosts.
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PMID:Icm/dot-independent entry of Legionella pneumophila into amoeba and macrophage hosts. 1527 14

Killing of Legionella pneumophila by an antimicrobial ceramic was evaluated during culture in nine kinds of hot spring water at 40 degrees C. After 24 hours, the efficacy against L. pneumophila varied, depended on water quality. The strongest antibacterial effect was seen in chloride hot spring water from Wakayama and in deionized water. In four hot spring water samples (sulfur and hydrogen carbonate springs from Fukushima, simple thermals from Mie, and radioactive spring from Tottori), the decrease was < -2 log cfu after 48 hours. These results suggest that the antimicrobial ceramic is able to eradicate Legionella from hot spring waters.
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PMID:[Antimicrobial ceramic for killing Legionella pneumophila in hot spring waters]. 1597 55

The efficiency of various disinfection treatments against Legionella was tested on a hot water distribution system (HWDS) pilot unit. The results demonstrated clearly that most Legionella in the networks were fixed in the biofilm at the surface of the pipe (more than 98% for each loop). Chemical treatments (continuous chlorination, hyperchlorination, hydrogen peroxide and peracetic acid mixing) commonly used for the eradication of Legionella in hot water distribution networks appeared to be inadequate for eradicating the bacteria in the biofilm. Unfortunately, the biofilm contained most of the pathogens in an HWDS whereas legislation is only restricted to the Legionella concentration in the water phase. Thermal treatment appeared to be efficient to disinfect most of the biofilm but seemed to promote the biofilm re-growth as well. It was then concluded that the best solution to prevent Legionella contamination in hot water distribution systems would be to have perfect control of the temperature in the networks (temperature > 55 degrees C at all points). Nevertheless, in many cases it is difficult to have such control, so during the time necessary to modify networks, the best solution to control Legionella proliferation appears to be to apply a treatment shock (thermal or chlorination as a function of pipe characteristics). These treatments must be followed by a continuous chlorination that is totally controlled and equipped with alarm systems. This study demonstrates that biofilm sampling devices must be installed in hot water distribution systems to anticipate Legionella contamination and correctly determine the efficiency of the treatments.
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PMID:Resistance of Legionella to disinfection in hot water distribution systems. 1631 47

Legionella pneumophila expresses two catalase-peroxidase enzymes that exhibit strong peroxidatic but weak catalatic activities, suggesting that other enzymes participate in decomposition of hydrogen peroxide (H2O2). Comparative genomics revealed that L. pneumophila and its close relative Coxiella burnetii each contain two peroxide-scavenging alkyl hydroperoxide reductase (AhpC) systems: AhpC1, which is similar to the Helicobacter pylori AhpC system, and AhpC2 AhpD (AhpC2D), which is similar to the AhpC AhpD system of Mycobacterium tuberculosis. To establish a catalatic function for these two systems, we expressed L. pneumophila ahpC1 or ahpC2 in a catalase/peroxidase mutant of Escherichia coli and demonstrated restoration of H2O2 resistance by a disk diffusion assay. ahpC1::Km and ahpC2D::Km chromosomal deletion mutants were two- to eightfold more sensitive to H2O2, tert-butyl hydroperoxide, cumene hydroperoxide, and paraquat than the wild-type L. pneumophila, a phenotype that could be restored by trans-complementation. Reciprocal strategies to construct double mutants were unsuccessful. Mutant strains were not enfeebled for growth in vitro or in a U937 cell infection model. Green fluorescence protein reporter assays revealed expression to be dependent on the stage of growth, with ahpC1 appearing after the exponential phase and ahpC2 appearing during early exponential phase. Quantitative real-time PCR showed that ahpC1 mRNA levels were approximately 7- to 10-fold higher than ahpC2D mRNA levels. However, expression of ahpC2D was significantly increased in the ahpC1 mutant, whereas ahpC1 expression was unchanged in the ahpC2D mutant. These results indicate that AhpC1 or AhpC2D (or both) provide an essential hydrogen peroxide-scavenging function to L. pneumophila and that the compensatory activity of the ahpC2D system is most likely induced in response to oxidative stress.
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PMID:Compensatory functions of two alkyl hydroperoxide reductases in the oxidative defense system of Legionella pneumophila. 1692 90

To survive in host cells, intracellular pathogens or symbiotic bacteria require protective mechanisms to overcome the oxidative stress generated by phagocytic activities of the host. By genomic library tagging, we cloned a dps (stands for DNA-binding protein from starved cells) gene of the symbiotic "Candidatus Legionella jeonii" organism (called the X bacterium) (dps(X)) that grows in Amoeba proteus. The gene encodes a 17-kDa protein (pI 5.19) with 91% homology to Dps and DNA-binding ferritin-like proteins of other organisms. The cloned gene complemented the dps mutant of Escherichia coli and conferred resistance to hydrogen peroxide. Dps(X) proteins purified from E. coli transformed with the dps(X) gene were in oligomeric form, formed a complex with pBlueskript SKII DNA, and protected the DNA from DNase I digestion and H(2)O(2)-mediated damage. The expression of the dps(X) gene in "Candidatus Legionella jeonii" was enhanced when the host amoeba was treated with 2 mM H(2)O(2) and by phagocytic activities of the host cell. These results suggested that the Dps protein has a function protective of the bacterial DNA and that its gene expression responds to oxidative stress generated by phagocytic activities of the host cell. With regard to the fact that invasion of Legionella sp. into respiratory phagocytic cells causes pneumonia in mammals, further characterization of dps(X) expression in the Legionella sp. that multiplies in a protozoan host in the natural environment may provide valuable information toward understanding the protective mechanisms of intracellular pathogens.
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PMID:The dps gene of symbiotic "Candidatus Legionella jeonii" in Amoeba proteus responds to hydrogen peroxide and phagocytosis. 1695 Sep 18

Legionella pneumophila expresses two peroxide-scavenging alkyl hydroperoxide reductase systems (AhpC1 and AhpC2D) that are expressed differentially during the bacterial growth cycle. Functional loss of the postexponentially expressed AhpC1 system is compensated for by increased expression of the exponentially expressed AhpC2D system. In this study, we used an acrylamide capture of DNA-bound complexes (ACDC) technique and mass spectrometry to identify proteins that bind to the promoter region of the ahpC2D operon. The major protein captured was an ortholog of OxyR (OxyR(Lp)). Genetic studies indicated that oxyR(Lp) was an essential gene expressed postexponentially and only partially complemented an Escherichia coli oxyR mutant (GS077). Gel shift assays confirmed specific binding of OxyR(Lp) to ahpC2D promoter sequences, but not to promoters of ahpC1 or oxyR(Lp); however, OxyR(Lp) weakly bound to E. coli OxyR-regulated promoters (katG, oxyR, and ahpCF). DNase I protection studies showed that the OxyR(Lp) binding motif spanned the promoter and transcriptional start sequences of ahpC2 and that the protected region was unchanged by treatments with reducing agents or hydrogen peroxide (H(2)O(2)). Moreover, the OxyR(Lp) (pBADLpoxyR)-mediated repression of an ahpC2-gfp reporter construct in E. coli GS077 (the oxyR mutant) was not reversed by H(2)O(2) challenge. Alignments with other OxyR proteins revealed several amino acid substitutions predicted to ablate thiol oxidation or conformational changes required for activation. We suggest these mutations have locked OxyR(Lp) in an active DNA-binding conformation, which has permitted a divergence of function from a regulator of oxidative stress to a cell cycle regulator, perhaps controlling gene expression during postexponential differentiation.
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PMID:An ortholog of OxyR in Legionella pneumophila is expressed postexponentially and negatively regulates the alkyl hydroperoxide reductase (ahpC2D) operon. 1835 10

Fast, sensitive, and especially, multianalyte test systems are currently of high interest for the monitoring and quality control of drinking water, since traditional microbiological methods are labor intensive and can take days until a response is achieved. In this study, the first flow-through chemiluminescence microarray was developed and characterized for the rapid and simultaneous detection of Escherichia coli O157:H7, Salmonella typhimurium, and Legionella pneumophila in water samples using a semiautomated readout system. Therefore, antibody microarrays were produced on poly(ethylene glycol)-modified glass substrates by means of a contact arrayer. For capturing bacteria, species-specific polyclonal antibodies were used. Cell recognition was carried out by binding of species-specific biotinylated antibodies. Chemiluminescence detection was accomplished by a streptavidin-horseradish peroxidase (HRP) catalyzed reaction of luminol and hydrogen peroxide. The chemiluminescence reaction that occurred was recorded by a sensitive charge-coupled device (CCD) camera. The overall assay time was 13 min, enabling a fast sample analysis. In multianalyte experiments, the detection limits were 3 x 10(6), 1 x 10(5), and 3 x 10(3) cells/mL for S. typhimurium, L. pneumophila, and E. coli O157:H7, respectively. Quantification of samples was possible in a wide concentration range with good recoveries. The presented system is well suited for quick and automatic water analysis.
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PMID:Detection of Escherichia coli O157:H7, Salmonella typhimurium, and Legionella pneumophila in water using a flow-through chemiluminescence microarray readout system. 1857 2

Ofloxacin ((+/-)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2, 3-dihydro-7H-pyrido[1,2,3-de]-1, 4-benzoxazine-6-carboxylic acid) is a totally synthetic fluoroquinolone antimicrobial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical pathogens such as Mycoplasma, Chlamydia and Legionella. Even though it is widely used for the treatment of gastrointestinal, pulmonary, urinary, and other infections, the comprehensive mechanism of action at molecular level has not been known so far. It is very important to understand the structural characteristics of the drug and the effects that are caused by the environments. With the purpose of deeply investigating the structure of Ofloxacin, an analog of Ofloxacin, Methyl-Ofloxacin (Me-OFL), was synthesized by methylation of 4'N in piperazine ring from Ofloxacin with CH3I. Then appropriate Me-OFL was dissolved in DC1/D2O and NaOH/D2O to prepare corresponding acidic and alkaline solutions. Systematic NMR spectroscopic investigation on Me-OFL in both acidic and alkaline solution was conducted using quantitative 1H and 13C spectra, DEPT, HSQC together with HMBC techniques. The spectra were recorded with Bruker AM-300 spectrometer and DRX500 spectrometer. Chemical shifts have been given in values referred to dioxane (deltaJ = 3.7, deltac = 67.8). Complete assignments on 1H and 13C signals of Me-OFL were obtained in different pH environments where the coupling constant between 13 C and 19F was found to be very helpful for the assignment of aromatic 13C signals. A comprehensive comparison between the 1H, 13C chemical shifts, together with the structural transformation in acidic and alkaline solutions was made and discussed in details. Due to the formation of hydrogen bond between COOH and C==O, the COOH and aromatic ring are in the same plane. As a result, a weak O...H--C hydrogen bond forms between C==O from the carboxyl group and 5-H from aromatic ring. In alkaline solution, the deprivation of H+ from COOH destroys not only the hydrogen bond between COOH and carbonyl group but also the weak hydrogen between the C==O from COOH and 5H. As a result, the 5H exhibited remarkable shift toward high field (1.02). Meanwhile, the chemical shift of 6C, 13C, 7C, 15C also exhibited remarkable shift to low field at 12. 04, 7.46, 4.33, 2.88 respectively. Such variations were related to the changes of p electrons from carboxyl group caused by the transformation between the carboxyl group and the carboxylate group in different pH environments. Comparison of deltaH, deltac data between Me-OFL and OFL in acidic solution and OFL in alkaline was made. In Me-OFL acidic solution, the chemical shift of 3'C, 5'C, 7'C, 8'C also exhibited remarkable shift to low field at 6.66-7.32 respectively, the chemical shift of 2'C and 6'C also exhibited remarkable shift to high field 6.04. In OFL acidic solution, the chemical shift of 2'C, 3'C, 5'C, 6'C, 7'C, 8'C also exhibited remarkable shift to high field within 2.39, Comparison between the protonation and the methylation on the 4'N atom from the piperazine ring was also made. The distribution of positive charge also showed difference. When protonation occurred on the piperazine ring, the positive charge was on the proton connected with 4'N. However, if methylation occurred, the positive charge is on the 4'-N atom.
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PMID:[A study on the NMR spectrum of methyl-ofloxacin]. 1880 Jul 40


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