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registries in rheumatoid arthritis and autoimmune diseases: data from the french registries.clinical registries have shown their effectiveness in capturing the long-term benefit of drugs in routine care. in france, two types of registry have been established to analyse the safety and efficacy of biological agents.201121148156
redundant and unique roles of coronin proteins in dictyostelium.dictyostelium discoideum harbors a short (crn12) and a long coronin (crn7) composed of one and two beta-propellers, respectively. they are primarily present in the cell cortex and cells lacking crn12 (cora⁻) or crn7 (corb⁻) have defects in actin driven processes. we compared the characteristics of a mutant cell line (cora⁻/corb⁻) lacking crn12 and crn7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. cytokinesis, uptake of small particles, and developmen ...201120640912
legionella pneumophila-induced iκbζ-dependent expression of interleukin-6 in lung epithelium.severe community- and hospital-acquired pneumonia is caused by legionella pneumophila. lung airway and alveolar epithelial cells comprise an important sentinel system in airborne infections. although interleukin (il)-6 is known as a central regulator of the immune response in pneumonia, its regulation in the lung is widely unknown. herein, we demonstrate that different l. pneumophila strains induce delayed expression of il-6 in comparison with il-8 by human lung epithelial cells. il-6 expression ...201120650996
parameters predictive of legionella contamination in hot water systems: association with trace elements and heterotrophic plate counts.the contamination of hot water samples with legionella spp. was studied in relation to temperature, total hardness, trace element concentrations (iron, zinc, manganese, and copper) and heterotrophic plate counts (hpc) at both 22 and 37 °c. factor analysis and receiver operating characteristic (roc) curves were used to establish the cut-off of water parameters as predictors for legionella contamination. legionella spp. was isolated in 194 out of 408 samples (47.5%), with legionella pneumophila be ...201121316728
protein kinase legk2 is a type iv secretion system effector involved in endoplasmic reticulum recruitment and intracellular replication of legionella pneumophila.legionella pneumophila is the etiological agent of legionnaires' disease. crucial to the pathogenesis of this intracellular pathogen is its ability to subvert host cell defenses, permitting intracellular replication in specialized vacuoles within host cells. the dot/icm type iv secretion system (t4ss), which translocates a large number of bacterial effectors into host cell, is absolutely required for rerouting the legionella phagosome. many legionella effectors display distinctive eukaryotic dom ...201121321072
quantification of viable legionella pneumophila cells using propidium monoazide combined with quantitative pcr.one of the greatest challenges of implementing fast molecular detection methods as part of legionella surveillance systems is to limit detection to live cells. in this work, a protocol for sample treatment with propidium monoazide (pma) in combination with quantitative pcr (qpcr) has been optimized and validated for l. pneumophila as an alternative of the currently used time-consuming culture method. results from pma-qpcr were compared with culture isolation and traditional qpcr. under the condi ...201121329735
[diversity of legionella pneumophila in cooling towers: coculture kinetics and virulence studies].legionella pneumophila (l. pneumophila) was isolated from three cooling towers involved in three community outbreaks of legionnaires´ disease. each cooling tower had two different chromosomal dna subtypes. however, only one matched identically to the clinical strains. to try to understand why only one of the environmental strains caused clinical cases we investigated the intrinsic virulence of these strains.201121339025
evaluation of an immunomagnetic separation assay in combination with cultivation to improve legionella pneumophila serogroup 1 recovery from environmental samples.aims: legionella isolation from environmental samples is often difficult because of the presence of heterotrophic-associated bacteria that frequently overgrow when using standard culture (iso 11731, 1998; nf t90-431, 2003) methods. to improve legionella pneumophila recovery from complex water samples (water from cooling towers, biofilms), we evaluated an immunomagnetic separation (ims) assay using a monoclonal antibody raised against the lipopolysaccharide of leg. pneumophila sg1 in combination ...201121276145
an international trial of quantitative pcr for monitoring legionella in artificial water systems.aims: to perform an international trial to derive alert and action levels for the use of quantitative pcr (qpcr) in the monitoring of legionella to determine the effectiveness of control measures against legionellae. methods and results: laboratories (7) participated from six countries. legionellae were determined by culture and qpcr methods with comparable detection limits. systems were monitored over =10 weeks. for cooling towers (232 samples), there was a significant difference between the ...201121276147
development of a dna microarray for detection and identification of legionella pneumophila and ten other pathogens in drinking water.the safety and accessibility of drinking water are major concerns throughout the world. consumption of water contaminated with infectious agents, toxic chemicals or radiological hazards represents a significant health risk and is strongly associated with mortality. therefore, we have developed an oligonucleotide-based microarray using the sequences of 16s-23s rdna internal transcribed spacer regions (its) and the gyrase subunit b gene (gyrb) found in the most prevalent and devastating waterborne ...201121276629
legionella pneumophila lbtu acts as a novel, tonb-independent receptor for the legiobactin siderophore.gram-negative legionella pneumophila produces a siderophore (legiobactin) that promotes lung infection. we previously determined that lbta and lbtb are required for the synthesis and secretion of legiobactin. dna sequence and reverse transcription-pcr (rt-pcr) analyses now reveal the presence of an iron-repressed gene (lbtu) directly upstream of the lbtab-containing operon. in silico analysis predicted that lbtu is an outer membrane protein consisting of a 16-stranded transmembrane ß-barrel, mul ...201121278293
differential requirements for naip5 in activation of the nlrc4 inflammasome.inflammasomes are cytosolic multiprotein complexes that assemble in response to infectious or noxious stimuli and activate the caspase-1 protease. the inflammasome containing the nucleotide binding domain-leucine-rich repeat (nbd-lrr) protein nlrc4 (interleukin-converting enzyme protease-activating factor [ipaf]) responds to the cytosolic presence of bacterial proteins such as flagellin or the inner rod component of bacterial type iii secretion systems (e.g., salmonella prgj). in some instances, ...201121282416
bacterial pathogenesis: legionella effector under friendly fire. 201121287709
legionella pneumophila type ii secretion dampens the cytokine response of infected macrophages and epithelia.the type ii secretion (t2s) system of legionella pneumophila is required for the ability of the bacterium to grow within the lungs of a/j mice. by utilizing mutants lacking t2s (lsp), we now document that t2s promotes the intracellular infection of both multiple types of macrophages and lung epithelia. following infection of macrophages, lsp mutants (but not a complemented mutant) elicited significantly higher levels of interleukin 6 (il-6), tumor necrosis factor alpha (tnf-+¦), il-10, il-8, il- ...201121383054
secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent legionella pneumophila.the intracellular bacterial pathogen legionella pneumophila causes an inflammatory pneumonia called legionnaires' disease. for virulence, l. pneumophila requires a dot/icm type iv secretion system that translocates bacterial effectors to the host cytosol. l. pneumophila lacking the dot/icm system is recognized by toll-like receptors (tlrs), leading to a canonical nf-+¦b-dependent transcriptional response. in addition, l. pneumophila expressing a functional dot/icm system potently induces unique ...201121390206
the professional phagocyte dictyostelium discoideum as a model host for bacterial pathogens.the use of simple hosts such as dictyostelium discoideum in the study of host pathogen interactions offers a number of advantages and has steadily increased in recent years. infection-specific genes can often only be studied in a very limited way in man and even in the mouse model their analysis is usually expensive, time consuming and technically challenging or sometimes even impossible. in contrast, their functional analysis in d. discoideum and other simple model organisms is often easier, fa ...201121366522
dsba2 (27 kda com1-like protein) of legionella pneumophila catalyses extracytoplasmic disulphide-bond formation in proteins including the dot/icm type iv secretion system.in gram-negative bacteria, thiol oxidoreductases catalyse the formation of disulphide bonds (dsb) in extracytoplasmic proteins. in this study, we sought to identify dsb-forming proteins required for assembly of macromolecular structures in legionella pneumophila. here we describe two dsb-forming proteins, one annotated as dsba1 and the other annotated as a 27 kda outer membrane protein similar to com1 of coxiella burnetii, which we designate as dsba2. both proteins are predicted to be periplasmi ...201121375592
retraction. inhibition of akt/gsk3ß signalling pathway by legionella pneumophila is involved in induction of t-cell apoptosis. 201121348858
characterisation of legionella pneumophila phospholipases and their impact on host cells.phospholipases are a diverse class of enzymes produced both by eukaryotic hosts and their pathogens. major insights into action pathways of bacterial phospholipases have been provided during the last years. on the one hand bacterial phospholipases act as potent membrane destructors and on the other hand they manipulate and initiate host signalling paths, such as chemokine expression or the inflammatory cascade. reaction products of bacterial phospholipases may potentially influence many more hos ...201121342713
activities of tigecycline and comparators against legionella pneumophila and legionella micdadei extracellularly and in human monocyte-derived macrophages.the activity of tigecycline against legionellae, which are intracellular pathogens, was evaluated intracellularly in human phagocytes and extracellularly, and compared to the activities of erythromycin and levofloxacin. clinical isolates of l. pneumophila serogroups 1, 5, and 6 and l. micdadei were tested in time-kill experiments. extracellular experiments were done using buffered yeast extract broth. for intracellular assays, monolayers of human monocyte-derived macrophages (mdm) were infected ...201121146719
clinical potential of diagnostic methods for the rapid diagnosis of mycoplasma pneumoniae pneumonia in adults.the purpose of the present study was to evaluate the accuracy and usefulness of three rapid diagnostic methods, immunocard mycoplasma kit, chest high-resolution computed tomography (hrct) findings, and the japanese respiratory society (jrs) scoring system (including six parameters), for the early presumptive diagnosis of mycoplasma pneumoniae pneumonia in adults. we performed three rapid diagnostic methods at the same time in four pneumonia groups: 68 cases with m. pneumoniae pneumonia, 133 case ...201121061035
Evaluation of the SD Bioline test, a new assay for detecting Legionella pneumophila serogroup 1 antigen in urine. 201222024377
respiratory syncytial virus (rsv) community-acquired pneumonia (cap) in a hospitalized adult with human immunodeficiency virus (hiv) mimicking influenza a and pneumocystis (carinii) jiroveci pneumonia (pcp).respiratory syncytial virus (rsv) is an important cause of lower respiratory tract infections in young children, the elderly, and immunocompromised hosts, but rsv is a rare cause of community-acquired pneumonia (cap) in hospitalized adults with human immunodeficiency virus (hiv). in patients with hiv, cap is most frequently attributable to the usual bacterial respiratory pathogens that cause cap in immunocompetent hosts, eg, streptococcuspneumoniae or hemophilus influenzae. adults with hiv are a ...201222005289
Caenorhabditis elegans as an Alternative Model to Study Senescence of Host Defense and the Prevention by Immunonutrition.Whether nutritional control can retard senescence of immune function and decrease mortality from infectious diseases has not yet been established; the difficulty of establishing a model has made this a challenging topic to investigate. Caenorhabditis elegans has been extensively used as an experimental system for biological studies. Particularly for aging studies, the worm has the advantage of a short and reproducible life span. The organism has also been recognized as an alternative to mammalia ...201222127882
Wild-type MIC distribution and epidemiological cut-off values in clinical Legionella pneumophila serogroup 1 isolates.The purpose of this study was to establish wild-type (WT) distributions and determine the epidemiological cut-off values (ECOFF) in clinical L. pneumophila serogroup 1 isolates for 10 antimicrobials commonly used for the treatment of Legionella infections using a method feasible in a routine clinical laboratory.201222100012
legionella longbeachae and endocarditis.we report a case of infectious endocarditis attributable to legionella longbeachae. l. longbeachae is usually associated with lung infections. it is commonly found in composted waste wood products. l. longbeachae should be regarded as an agent of infectious endocarditis, notably in the context of gardening involving handling of potting soils.201222261182
legionella micdadei prosthetic valve endocarditis complicated by brain abscess: case report and review of the literature.legionella endocarditis is extremely uncommon, and embolic phenomena have never been reported. we report the first case of legionella micdadei prosthetic valve endocarditis complicated by brain abscess. a 57-y-old immunocompromised woman with a history of mitral valve replacement developed confusion and left-sided weakness. brain magnetic resonance imaging showed a 3-cm peripheral-enhancing mass. transoesophageal echocardiography suggested a perivalvular abscess. blood cultures and valve culture ...201222235842
innate immune pathways triggered by listeria monocytogenes and their role in the induction of cell-mediated immunity.acquired cell-mediated immunity to listeria monocytogenes is induced by infection with live, replicating bacteria that grow in the host cell cytosol, whereas killed bacteria, or those trapped in a phagosome, fail to induce protective immunity. in this chapter, we focus on how l. monocytogenes is sensed by the innate immune system, with the presumption that innate immunity affects the development of acquired immunity. infection by l. monocytogenes induces three innate immune pathways: an myd88-de ...201222244582
domain structure and denaturation of a dimeric mip-like peptidyl prolyl cis-trans isomerase from escherichia coli.fkbp22, a protein expressed by escherichia coli, possesses ppiase (peptidyl-prolyl cis-trans isomerase) activity, binds fk506 (an immunosuppressive drug) and shares homology with legionella mip (a virulence factor) and the related proteins. to understand the domain structure and the folding / unfolding mechanism of mip-like proteins, a recombinant e. coli fkbp22 (his-fkbp22) was investigated here as a model protein. limited proteolysis indicated that his-fkbp22 harbors an n-terminal domain (ntd) ...201222263615
legionella pneumophila secretes a mitochondrial carrier protein during infection.the mitochondrial carrier family (mcf) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. mcf proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. we discovered a novel mcf member, termed legionellanucleotide carrier protein (lncp), encoded in the genome of legionella pneumophila, the causative agent of legionnaire's disease. lncp was se ...201222241989
an outbreak of legionnaires disease associated with a decorative water wall fountain in a hospital.objective. to detect an outbreak-related source of legionella, control the outbreak, and prevent additional legionella infections from occurring. design and setting. epidemiologic investigation of an acute outbreak of hospital-associated legionnaires disease among outpatients and visitors to a wisconsin hospital. patients. patients with laboratory-confirmed legionnaires disease who resided in southeastern wisconsin and had illness onsets during february and march 2010. methods. patients with ...201222227989
live legionella pneumophila induces muc5ac production by airway epithelial cells independently of intracellular invasion.the airway epithelium is the initial barrier against airborne pathogens, and it plays many roles in host airway defense. legionella pneumophila is an intracellular pathogen that causes rapidly advancing pneumonia and is sometimes life-threatening. here, we evaluated the role of the airway epithelial cells in the defense against l. pneumophila by examining mucus production in vitro. the production of muc5ac, a major mucin protein, was not induced by formalin- or ultraviolet-killed l. pneumophil ...201222260247
legionella pneumophila lida affects nucleotide binding and activity of the host gtpase rab1.legionella pneumophila, the causative agent of a severe pneumonia known as legionnaires' disease, intercepts material from host cell membrane transport pathways to create a specialized vacuolar compartment that supports bacterial replication. delivery of bacterial effector proteins into the host cell requires the dot/icm type iv secretion system. several effectors, including sidm, sidd, and lepb, were shown to target the early secretory pathway by manipulating the activity of the host guanosine ...201222228731
inhibition of bacterial carbonic anhydrases and zinc proteases: from orphantargets to innovative new antibiotic drugs.zinc-containing enzymes, such as carbonic anhydrases (cas) and metalloproteases (mps) play critical functions in bacteria, being involved in various steps of their life cycle, which are important for survival, colonization, acquisition of nutrients for growth and proliferation, facilitation of dissemination, invasion and pathogenicity. the development of resistance to many classes of clinically used antibiotics emphasizes the need of new antibacterial drug targets to be explored. there is a weal ...201222214451
eight years of legionnaires' disease transmission in travellers to a condominium complex in las vegas, nevada.summarytravel is a risk factor for legionnaires' disease. in 2008, two cases were reported in condominium guests where we investigated a 2001 outbreak. we reinvestigated to identify additional cases and determine whether ongoing transmission resulted from persistent colonization of potable water. exposures were assessed by matched case-control analyses (2001) and case-series interviews (2008). we sampled potable water and other water sources. isolates were compared using sequence-based typing. f ...201222214820
legionella secreted effectors and innate immune responses.legionella pneumophila is a facultative intracellular pathogen capable of replicating in a wide spectrum of cells. successful infection by legionella requires the dot/icm type iv secretion system, which translocates a large number of effector proteins into infected cells. by co-opting numerous host cellular processes, these proteins function to establish a specialized organelle that allows bacterial survival and proliferation. even within the vacuole, l. pneumophila triggers robust immune respon ...201221985602
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