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)

L-arginine-dependent reactive nitrogen intermediates have been identified as macrophage cytotoxic effector molecules against intracellular pathogens. To determine its role, ex vivo production of NO by peritoneal macrophages of C3H/HeN mice and Dunkin-Hartley guinea pigs infected intraperitoneally with a virulent and isogenic avirulent Legionella pneumophila serogroup 1 strain was compared with bacterial clearance from the lungs. While the virulent strain was cleared from mice lungs, the guinea pigs died within 96 h. In vivo infection with both strains resulted in the production of NO by mouse peritoneal macrophages ex vivo. In contrast, guinea pig macrophages did not produce detectable NO. In addition, infection by the avirulent strain led to the production of significantly more NO by mouse macrophages than the virulent parent strain, irrespective of stimulation with lipopolysaccharide (LP) and/or interferon-gamma (ifn-gamma). These results suggest that resistance to Leg. pneumophila infection may depend on the production of NO by host macrophages.
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PMID:Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1. 860 33

To facilitate identification of the effector mechanism(s) responsible for gamma interferon (IFN-gamma)-mediated host resistance to Legionella pneumophila, a murine model of legionellosis in BALB/c mice with a targeted disruption in the IFN-gamma gene (gamma knockout [GKO] mice) was developed. Immunocompetent BALB/c mice and GKO mice were inoculated intratracheally with virulent L. pneumophila (10(6) bacteria per mouse), and bacterial clearance and the pulmonary inflammatory response were assessed. L. pneumophila did not replicate in, and was rapidly cleared from, the lungs of immunocompetent BALB/c mice, demonstrating that immunocompetent BALB/c mice are resistant to replicative L. pneumophila pulmonary infections. In contrast, similarly infected GKO mice developed persistent, replicative intrapulmonary L. pneumophila infections with extrapulmonary dissemination of the bacteria to the spleen. Histopathologic and flow cytometric analysis of L. pneumophila-infected lung tissue demonstrated that while immunocompetent BALB/c mice develop multifocal pneumonitis which resolves, similarly infected GKO mice develop diffuse pneumonitis with persistent neutrophil recruitment into the lung. Intratracheal administration of exogenous IFN-gamma to L. pneumophila-infected GKO mice facilitated intrapulmonary clearance of the bacteria, confirming the pivotal role of IFN-gamma in innate host defenses to L. pneumophila lung infection in this murine host. The potential role of endogenous reactive nitrogen intermediates, including nitric oxide (NO), in IFN-gamma-mediated resistance to L. pneumophila pulmonary infections in immunocompetent BALB/c mice was subsequently assessed. Macrophage inducible nitric oxide synthetase (an enzyme responsible for the production of NO) was induced in alveolar cells from L. pneumophila-infected immunocompetent BALB/c mice (with maximal expression at 48 h postinfection) but was not induced in similarly infected GKO mice. However, administration of the NO synthetase inhibitor N-monomethyl-L-arginine did not significantly inhibit clearance of L. pneumophila from the lung of immunocompetent BALB/c mice (compared with that in similarly infected mice not administered N-monomethyl-L-arginine). In contrast, we have previously demonstrated that IFN-gamma-induced host resistance to replicative L. pneumophila lung infections in a susceptible murine host (A/J mice) is mediated, in part, by endogenous NO. Taken together, these studies identify a differing role of endogenous NO in IFN-gamma-mediated resistance to L. pneumophila pulmonary infection in susceptible and resistant murine hosts.
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PMID:Effector mechanisms responsible for gamma interferon-mediated host resistance to Legionella pneumophila lung infection: the role of endogenous nitric oxide differs in susceptible and resistant murine hosts. 894 59

The structure of the lipid A from Rhizobium etli and Rhizobium leguminosarum lipopolysaccharides (LPSs) lacks phosphate and contains a galacturonosyl residue at its 4' position, an acylated 2-aminogluconate in place of the proximal glucosamine, and a very long chain omega-1 hydroxy fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0). The 27OHC28:0 moiety is common in lipid A's among members of the Rhizobiaceae and also among a number of the facultative intracellular pathogens that form chronic infections, e.g., Brucella abortus, Bartonella henselae, and Legionella pneumophila. In this paper, a mutant of R. leguminosarum was created by placing a kanamycin resistance cassette within acpXL, the gene which encodes the acyl carrier protein for 27OHC28:0. The result was an LPS containing a tetraacylated lipid A lacking 27OHC28:0. A small amount of the mutant lipid A may contain an added palmitic acid residue. The mutant is sensitive to changes in osmolarity and an increase in acidity, growth conditions that likely occur in the nodule microenvironment. In spite of the probably hostile microenvironment of the nodule, the acpXL mutant is still able to form nitrogen-fixing root nodules even though the appearance and development of nodules are delayed. Therefore, it is possible that the acpXL mutant has a host-inducible mechanism which enables it to adapt to these physiological changes.
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PMID:A Rhizobium leguminosarum AcpXL mutant produces lipopolysaccharide lacking 27-hydroxyoctacosanoic acid. 1261 48

Lipid A of Rhizobium leguminosarum, a nitrogen-fixing plant endosymbiont, displays several significant structural differences when compared with Escherichia coli. An especially striking feature of R. leguminosarum lipid A is that it lacks both the 1- and 4'-phosphate groups. Distinct lipid A phosphatases that attack either the 1 or the 4' positions have previously been identified in extracts of R. leguminosarum and Rhizobium etli but not Sinorhizobium meliloti or E. coli. Here we describe the identification of a hybrid cosmid (pMJK-1) containing a 25-kb R. leguminosarum 3841 DNA insert that directs the overexpression of the lipid A 1-phosphatase. Transfer of pMJK-1 into S. meliloti 1021 results in heterologous expression of 1-phosphatase activity, which is normally absent in extracts of strain 1021, and confers resistance to polymyxin. Sequencing of a 7-kb DNA fragment derived from the insert of pMJK-1 revealed the presence of a lipid phosphatase ortholog (designated LpxE). Expression of lpxE in E. coli behind the T7lac promoter results in the appearance of robust 1-phosphatase activity, which is normally absent in E. coli membranes. Matrix-assisted laser-desorption/time of flight and radiochemical analysis of the product generated in vitro from the model substrate lipid IVA confirms the selective removal of the 1-phosphate group. These findings show that lpxE is the structural gene for the 1-phosphatase. The availability of lpxE may facilitate the re-engineering of lipid A structures in diverse Gram-negative bacteria and allow assessment of the role of the 1-phosphatase in R. leguminosarum symbiosis with plants. Possible orthologs of LpxE are present in some intracellular human pathogens, including Francisella tularensis, Brucella melitensis, and Legionella pneumophila.
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PMID:Expression cloning and biochemical characterization of a Rhizobium leguminosarum lipid A 1-phosphatase. 1286 41

Resistance to macrolides and beta-lactams has increased sharply amongst key respiratory pathogens, leading to major concern. A novel series of acylides was designed to overcome this resistance and was evaluated for in vitro and in vivo activity. This series of acylides was designed starting from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. Minimum inhibitory concentrations (MICs) of acylides were determined against susceptible as well as macrolide-lincosamide-streptogramin B (MLS(B))--and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes and Moraxella catarrhalis by the agar dilution method. Microbroth MICs for Haemophilus influenzae were determined according to Clinical and Laboratory Standards Institute guidelines. In vivo efficacy was determined by target organ load reduction against S. pneumoniae 3579 (ermB). The bactericidal potential of promising acylides was also determined. MICs of these compounds against S. pneumoniae, S. pyogenes, H. influenzae and M. catarrhalis were in the range of 0.06-2, 0.125-1, 1-16 and 0.015-0.5 microg/mL, respectively, irrespective of their resistance pattern. Mycoplasma pneumoniae and Legionella pneumophila showed MIC ranges of 0.004-0.125 microg/mL and 0.004-0.03 microg/mL, respectively. The acylides also showed better activity against telithromycin-resistant S. pneumoniae strains. Compounds with a 4-furan-2-yl-1H-imidazolyl side chain on the carbamate (RBx 10000296) showed a target organ load reduction of >3 log(10) colony-forming units/mL and concentration-dependent bactericidal potential against S. pneumoniae 994 mefA and H. influenzae strains. This novel and potent series of acylides active against antibiotic-resistant respiratory pathogens should be further investigated.
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PMID:Activity of a novel series of acylides active against community-acquired respiratory pathogens. 2049 66

The use of permeable pavement systems with integrated geothermal heat pumps for the treatment and recycling of urban runoff is novel and timely. This study assesses the efficiency of the combined technology for controlled indoor and uncontrolled outdoor experimental rigs. Water quality parameters such as biochemical oxygen demand, nutrients, total viable heterotrophic bacteria and total coliforms were tested before and after treatment in both rigs. The water borne bacterial community genomic deoxyribonucleic acid (DNA) was analyzed by polymerase chain reaction (PCR) amplification followed by denaturing gradient gel electrophoresis (DGGE) and was further confirmed by DNA sequencing techniques. Despite the relatively high temperatures in the indirectly heated sub-base of the pavement, potentially pathogenic organisms such as Salmonella spp., Escherichia coli, faecal Streptococci and Legionella were not detected. Moreover, mean removal rates of 99% for biochemical oxygen demand, 97% for ammonia-nitrogen and 95% for orthophosphate-phosphates were recorded. This research also supports decision-makers in assessing public health risks based on qualitative molecular microbiological data associated with the recycling of treated urban runoff.
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PMID:The synergy of permeable pavements and geothermal heat pumps for stormwater treatment and reuse. 2127 49

Rhizobium leguminosarum is a Gram-negative bacterium that forms nitrogen-fixing symbioses with compatible leguminous plants via intracellular invasion and establishes a persistent infection within host membrane-derived subcellular compartments. Notably, an unusual very-long-chain fatty acid (VLCFA) is found in the lipid A of R. leguminosarum as well as in the lipid A of the medically relevant pathogens Brucella abortus, Brucella melitensis, Bartonella henselae, and Legionella pneumophila, which are also able to persist within intracellular host-derived membranes. These bacterial symbionts and pathogens each contain a homologous gene region necessary for the synthesis and transfer of the VLCFA to the lipid A. Within this region lies a gene that encodes the specialized acyl carrier protein AcpXL, on which the VLCFA is built. This study describes the biochemical and infection phenotypes of an acpXL mutant which lacks the VLCFA. The mutation was created in R. leguminosarum bv. phaseoli strain 8002, which forms symbiosis with Phaseolus vulgaris, a determinate nodulating legume. Structural analysis using gas chromatography and mass spectrometry revealed that the mutant lipid A lacked the VLCFA. Compared to the parent strain, the mutant was more sensitive to the detergents deoxycholate and dodecyl sulfate and the antimicrobial peptide polymyxin B, suggesting a compromise to membrane stability. In addition, the mutant was more sensitive to higher salt concentrations. Passage through the plant restored salt tolerance. Electron microscopic examination showed that the mutant was developmentally delayed during symbiotic infection of the host plant Phaseolus vulgaris and produced abnormal symbiosome structures.
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PMID:An acpXL mutant of Rhizobium leguminosarum bv. phaseoli lacks 27-hydroxyoctacosanoic acid in its lipid A and is developmentally delayed during symbiotic infection of the determinate nodulating host plant Phaseolus vulgaris. 2176 36

RpkA (Receptor phosphatidylinositol kinase A) is an unusual seven-helix transmembrane protein of Dictyostelium discoideum with a G protein coupled receptor (GPCR) signature and a C-terminal lipid kinase domain (GPCR-PIPK) predicted as a phosphatidylinositol-4-phosphate 5-kinase. RpkA-homologs are present in all so far sequenced Dictyostelidae as well as in several other lower eukaryotes like the oomycete Phytophthora, and in the Legionella host Acanthamoeba castellani. Here we show by immunofluorescence that RpkA localizes to endosomal membranes and is specifically recruited to phagosomes. RpkA interacts with the phagosomal protein complex V-ATPase as proteins of this complex co-precipitate with RpkA-GFP as well as with the GST-tagged PIPK domain of RpkA. Loss of RpkA leads to a defect in phagocytosis as measured by yeast particle uptake. The uptake of the pathogenic bacterium Legionella pneumophila was however unaltered whereas its intra-cellular replication was significantly enhanced in rpkA(-). The difference between wild type and rpkA(-) was even more prominent when L. hackeliae was used. When we investigated the reason for the enhanced susceptibility for L. pneumophila of rpkA(-) we could not detect a difference in endosomal pH but rpkA(-) showed depletion of phosphoinositides (PIP and PIP(2)) when we compared metabolically labeled phosphoinositides from wild type and rpkA(-). Furthermore rpkA(-) exhibited reduced nitrogen starvation tolerance, an indicator for a reduced autophagy rate. Our results indicate that RpkA is a component of the defense system of D. discoideum as well as other lower eukaryotes.
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PMID:RpkA, a highly conserved GPCR with a lipid kinase domain, has a role in phagocytosis and anti-bacterial defense. 2207 13

The Neotropical detritivorous catfish Panaque nigrolineatus imbibes large quantities of wood as part of its diet. Due to the interest in cellulose, hemi-cellulose and lignin degradation pathways, this organism provides an interesting model system for the detection of novel microbial catabolism. In this study, we characterize the microbial community present in different regions of the alimentary tract of P. nigrolineatus fed a mixed diet of date palm and palm wood in laboratory aquaria. Analysis was performed on 16S rRNA gene clone libraries derived from anterior and posterior regions of the alimentary tract and the auxiliary lobe (AL), an uncharacterized organ that is vascularly attached to the midgut. Sequence analysis and phylogenetic reconstruction revealed distinct microbial communities in each tissue region. The foregut community shared many phylotypes in common with aquarium tank water and included Legionella and Hyphomicrobium spp. As the analysis moved further into the gastrointestinal tract, phylotypes with high levels of 16S rRNA sequence similarity to nitrogen-fixing Rhizobium and Agrobacterium spp. and Clostridium xylanovorans and Clostridium saccharolyticum, dominated midgut and AL communities. However, the hindgut was dominated almost exclusively by phylotypes with the highest 16S rRNA sequence similarity to the Cytophaga-Flavobacterium-Bacteroides phylum. Species richness was highest in the foregut (Chao(1) = 26.72), decreased distally through the midgut (Chao(1) = 25.38) and hindgut (Chao(1) = 20.60), with the lowest diversity detected in the AL (Chao(1) = 18.04), indicating the presence of a specialized microbial community. Using 16S rRNA gene phylogeny, we report that the P. nigrolineatus gastrointestinal tract possesses a microbial community closely related to microorganisms capable of cellulose degradation and nitrogen fixation. Further studies are underway to determine the role of this resident microbial community in Panaque nigrolineatus.
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PMID:Phylogenetic analysis of microbial communities in different regions of the gastrointestinal tract in Panaque nigrolineatus, a wood-eating fish. 2313 40

A taxonomic and annotated functional description of microbial life was deduced from 53 Mb of metagenomic sequence retrieved from a planktonic fraction of the Neotropical high Andean (3,973 meters above sea level) acidic hot spring El Coquito (EC). A classification of unassembled metagenomic reads using different databases showed a high proportion of Gammaproteobacteria and Alphaproteobacteria (in total read affiliation), and through taxonomic affiliation of 16S rRNA gene fragments we observed the presence of Proteobacteria, micro-algae chloroplast and Firmicutes. Reads mapped against the genomes Acidiphilium cryptum JF-5, Legionella pneumophila str. Corby and Acidithiobacillus caldus revealed the presence of transposase-like sequences, potentially involved in horizontal gene transfer. Functional annotation and hierarchical comparison with different datasets obtained by pyrosequencing in different ecosystems showed that the microbial community also contained extensive DNA repair systems, possibly to cope with ultraviolet radiation at such high altitudes. Analysis of genes involved in the nitrogen cycle indicated the presence of dissimilatory nitrate reduction to N2 (narGHI, nirS, norBCDQ and nosZ), associated with Proteobacteria-like sequences. Genes involved in the sulfur cycle (cysDN, cysNC and aprA) indicated adenylsulfate and sulfite production that were affiliated to several bacterial species. In summary, metagenomic sequence data provided insight regarding the structure and possible functions of this hot spring microbial community, describing some groups potentially involved in the nitrogen and sulfur cycling in this environment.
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PMID:Structural and functional insights from the metagenome of an acidic hot spring microbial planktonic community in the Colombian Andes. 2325 87


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