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)

Pathogenic Legionella pneumophila evolved as a parasite of aquatic amoebae. To persist in the environment, the microbe must be proficient at both replication and transmission. In laboratory cultures, as nutrients become scarce a stringent response-like pathway coordinates exit from the exponential growth phase with induction of traits correlated with virulence, including motility. A screen for mutants that express the flagellin gene poorly identified five activators of virulence: LetA/LetS, a two-component regulator homologous to GacA/GacS of Pseudomonas and SirA/BarA of Salmonella; the stationary-phase sigma factor RpoS; the flagellar sigma factor FliA; and a new locus, letE. Unlike wild type, post-exponential-phase letA and letS mutants were not motile, cytotoxic, sodium sensitive or proficient at infecting macrophages. L. pneumophila also required fliA to become motile, cytotoxic and to infect macrophages efficiently and letE to express sodium sensitivity and maximal motility and cytotoxicity. When induced to express RelA, all of the strains exited the exponential phase, but only wild type converted to the fully virulent form. In contrast, intracellular replication was independent of letA, letS, letE or fliA. Together, the data indicate that, as the nutrient supply wanes, ppGpp triggers a regulatory cascade mediated by LetA/ LetS, RpoS, FliA and letE that coordinates differentiation of replicating L. pneumophila to a transmissible form.
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PMID:A two-component regulator induces the transmission phenotype of stationary-phase Legionella pneumophila. 1196 72

The aim of this study was to identify the clinical features of Legionnaires' disease, sudden outbreaks of which demand a quick and flexible clinical approach, particularly with regard to diagnosis and therapy. A prospective and comparative study based on a clinical protocol was performed during an outbreak of Legionnaires' disease in Alcoy, Spain. The outbreak was environmental in origin, linked to cooling towers. Data about epidemiological and clinical features, blood chemistry values, radiological and microbiological findings, and characteristics related to the clinical course of Legionnaires' disease were obtained for 357 patients admitted to hospital with community-acquired pneumonia (177 with Legionella pneumonia). Patients with Legionnaires' disease were younger (mean age, 65.3+/-16.5 years) and more likely to be smokers compared with patients with other types of pneumonia (28.8% vs. 11.1%; P<0.01). Moreover, they had not been admitted to any hospital because of pneumonia in the previous year. Patients with Legionnaires' disease had higher fever, more severe headache, and less expectoration as well as lower sodium blood levels (mean, 132.6+/-4.8 mmol/l vs. 135.7 mmol/l; P<0.01). Radiological studies also showed that fewer patients with Legionnaires' disease had pleural effusion (9% vs. 19.4% of those with non- Legionella pneumonia). The presence of headache, high fever, hyponatremia, scanty or null expectoration, and current cigarette smoking provides physicians with important clues for a high suspicion of Legionella pneumonia before the results of confirmatory laboratory tests are available.
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PMID:Clinical study of an outbreak of Legionnaire's disease in Alcoy, Southeastern Spain. 1241 72

A 69-year-old man developed a cough and fever during treatment with corticosteroid (p.o. and external use) for erythroderma. Chest X-ray films revealed a consolidation shadow in the right upper lung field. Initial treatment with sulbactam sodium/ampicillin followed by imipenem/cilastatin was not effective. A urinary antigen test for Legionella was positive, making for a diagnosis of Legionella pneumonia. Intravenous treatment with ciprofloxacin (CPFX) was remarkably effective. His symptoms, chest X-ray and laboratory data rapidly improved after its initiation. Our findings strongly suggest that intravenous treatment with fluoroquinolones including CPFX should also be a first choice for Legionella pneumonia in Japan.
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PMID:Legionella pneumophila pneumonia successfully treated with intravenous ciprofloxacin. 1248 83

Legionella pneumophyla is the agent responsible of Legionnaire's disease. It appears as a severe pneumonia and often requires admission in Intensive Care Unit. In literature, renal failure is reported to occur in 15 percent of Legionnaire disease and this event induce a mortality over 50% of these cases. The authors describe a case of Legionnaire's pneumonia with respiratory failure, rhabdomyolysis and acute renal failure. Patient was a female, 61 yrs old, admitted to our hospital because of fever (38 degrees-38.5 degrees C), severe respiratory failure (pH = 7.49, PaCO2 = 23.1 mmHg, PaO2 = 56.7 mmHg), oliguria (< 200 ml/24 h); chest x-rays and computed tomography (TC) showed a pneumonia at right lower lobe. Among other things, in blood analysis was noted the following values: BUN = 47 mg/dl, creatinine = 2.1 mg/dl, Na+ = 133 mmol/L, Cl- = 97 mmol/L, Ca+ = 7.2 mg/dl, K+ = 5.8 mmol/L, AST = 213 U/L, ALT = 45 U/L, LDH = 1817 U/L, CPK = 16738 U/L, CPK-MB = 229 U/L, myoglobin > 4300 ng/ml., leucocyte count = 17,500/mmc (N = 92%, L = 3%, M = 5%), positive anti Legionella IgG and IgM (IgG > 1:64, IgM > 1:96), evidence of Legionella soluble antigen in the urine analysis. Therapy with clarytromicyne (500 mg b.i.d i.v.) and rifampicin (600 mg/die i.v.) was begun; computed tomography showed after six days an improvement of pulmonary lesion but, in the following days, health status and blood analysis got worse. Patient went on antibiotics and underwent haemotherapy (Hb: 8 gr/dl), haemodialysis because of acute renal failure but healthy status worse furthermore and she died on 18th days after admission. This case point out rhabdomyolysis with acute renal failure is suggestive for Legionnaire's disease and is associated with high rate of mortality.
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PMID:[Legionnaire's pneumonia with rhabdomyolysis and acute renal failure. A case report]. 1294 1

Legionella pneumophila can replicate inside amoebae and also alveolar macrophages to cause Legionnaires' Disease in susceptible hosts. When nutrients become limiting, a stringent-like response coordinates the differentiation of L. pneumophila to a transmissive form, a process mediated by the two-component system LetA/S and the sigma factors RpoS and FliA. Here we demonstrate that the broadly conserved RNA binding protein CsrA is a global repressor of L. pneumophila transmission phenotypes and an essential activator of intracellular replication. By analysing csrA expression and the phenotypes of csrA single and double mutants and a strain that expresses csrA constitutively, we demonstrate that, during replication in broth, CsrA represses every post-exponential phase phenotype examined, including cell shape shortening, motility, pigmentation, stress resistance, sodium sensitivity, cytotoxicity and efficient macrophage infection. At the transition to the post-exponential phase, LetA/S relieves CsrA repression to induce transmission phenotypes by both FliA-dependent and -independent pathways. For L. pneumophila to avoid lysosomal degradation in macrophages, CsrA repression must be relieved by LetA/S before phagocytosis; conversely, before intracellular bacteria can replicate, CsrA repression must be restored. The reciprocal regulation of replication and transmission exemplified by CsrA likely enhances the fitness of microbes faced with fluctuating environments.
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PMID:Legionella pneumophila CsrA is a pivotal repressor of transmission traits and activator of replication. 1461 70

Legionnaire's disease is caused by the intracellular pathogen Legionella pneumophila, presenting as an acute pneumonia. Attachment is the key step during infection, often relying on an interaction between host cell oligosaccharides and bacterial adhesins. Inhibition of this interaction by receptor mimics offers possible novel therapeutic treatments. L. pneumophila attachment to the A549 cell line was significantly reduced by treatment with tunicamycin (73.6%) and sodium metaperiodate (63.7%). This indicates the importance of cell surface oligosaccharide chains in adhesion. A number of putative anti-adhesion compounds inhibited attachment to the A549 and U937 cell lines. The most inhibitory compounds were polymeric saccharides, GalNAcbeta1-4Gal, Galbeta1-4GlcNAc and para-nitrophenol. These compounds inhibited adhesion to a range of human respiratory cell lines, including nasal epithelial, bronchial epithelial and alveolar epithelial cell lines and the human monocytic cell line, U937. Some eukaryotic receptors for L. pneumophila were determined to be the glycolipids, asialo-GM1 and asialo-GM2 that contain the inhibitory saccharide moiety, GalNAcbeta1-4Gal. The identified compounds have the potential to be used as novel treatments for Legionnaire's disease.
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PMID:Oligosaccharide receptor mimics inhibit Legionella pneumophila attachment to human respiratory epithelial cells. 1468 61

Legionella pneumophila utilizes a type IV secretion system (T4SS) encoded by 26 dot/icm genes to replicate inside host cells and cause disease. In contrast to all other L. pneumophila dot/icm genes, dotU and icmF have homologs in a wide variety of gram-negative bacteria, none of which possess a T4SS. Instead, dotU and icmF orthologs are linked to a locus encoding a conserved cluster of proteins designated IcmF-associated homologous proteins, which has been proposed to constitute a novel cell surface structure. We show here that dotU is partially required for L. pneumophila intracellular growth, similar to the known requirement for icmF. In addition, we show that dotU and icmF are necessary for optimal plasmid transfer and sodium sensitivity, two additional phenotypes associated with a functional Dot/Icm complex. We found that these effects are due to the destabilization of the T4SS at the transition into the stationary phase, the point at which L. pneumophila becomes virulent. Specifically, three Dot proteins (DotH, DotG, and DotF) exhibit decreased stability in a DeltadotU DeltaicmF strain. Furthermore, overexpression of just one of these proteins, DotH, is sufficient to suppress the intracellular growth defect of the DeltadotU DeltaicmF mutant. This suggests a model where the DotU and IcmF proteins serve to prevent DotH degradation and therefore function to stabilize the L. pneumophila T4SS. Due to their wide distribution among bacterial species and their genetic linkage to known or predicted cell surface structures, we propose that this function in complex stabilization may be broadly conserved.
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PMID:Legionella pneumophila DotU and IcmF are required for stability of the Dot/Icm complex. 1538 2

A 64-year-old man was referred to us because of pneumonia refractory to panipenem/betamipron. His chest radiography showed patchy consolidations in the lower lobe of the right lung and in the middle field of the left lung, and severe hypoxia was present. He was diagnosed as having acute respiratory distress syndrome due to severe pneumonia, and was treated with pulse methylprednisolone and sivelestat sodium in combination with intravenous erythromycin and ciprofloxacin. The patient recovered with this treatment. Serological examination using blood samples collected on the 12th and 28th hospital days revealed elevation of anti-L. pneumophila serogroup I antibody. It is suggested that administration of methylprednisolone and sivelestat sodium in combination with intravenous erythromycin and ciprofloxacin in a case of severe Legionella pneumonia complicated with acute respiratory distress syndrome is effective, and may be of use in similar cases.
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PMID:[A case of Legionella pneumonia complicated with acute respiratory distress syndrome treated with methylprednisolone and sivelestat sodium in combination with intravenous erythromycin and ciprofloxacin]. 1565 Dec 76

Differentiation in response to environmental cues is integral to the success of many intracellular pathogens. By characterizing a Legionella pneumophila mutant defective for differentiation in broth and replication in macrophages, we identified a subfamily of major facilitator superfamily transporters, here named Pht (phagosomal transporter), that also is conserved in two other vacuolar pathogens, Coxiella burnetii and Francisella tularensis. Biolog phenotype microarray analysis indicated that PhtA transports threonine, an essential amino acid. Either excess threonine or threonine peptides bypass phtA function. In minimal medium, phtA mutants do not replicate; in rich broth, the bacteria prematurely differentiate to the transmissive phase, as judged by the kinetics of flaA-gfp expression, heat resistance, and sodium sensitivity. PhtA is dispensable for transmissive L. pneumophila to establish and persist within a replication vacuole but is essential for their differentiation to the replicative phase, based on phenotypic and RT-PCR analysis. Accordingly, we propose that the Pht transporter family equips transmissive L. pneumophila, C. burnetii, and F. tularensis to assess their phagosomal nutrient supply before committing to reenter the cell cycle.
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PMID:The phagosomal transporter A couples threonine acquisition to differentiation and replication of Legionella pneumophila in macrophages. 1599 35

A bicarbonate-sulphate-calcic water of a therapeutic spa was monitored for the presence of Legionella, Pseudomonas and Mycobacteria. The water was analysed by taking samples from the well, the feed tank and from the final aerosol generating devices of two different water lines, the former at 21-23 degrees, the second at 36-38 degrees. The bacteria in question were always absent from the well. Legionellae were found in the water of aerosol equipment: Legionella micdadei was isolated from 75% of samples, L. bozemanii from 75% and 50% (respectively 36-38 degrees and 21-22 degrees water lines) and other species of environmental Legionellae from 25% of samples. The water of aerosol equipment presented high total bacterial counts (10(3)-10(4) cfu/ml) and exspecially high concentrations of Pseudomonadaceae (10(2)-10(3) cfu/100 ml). These bacteria, unlike the Legionellae, were also isolated from the feed tank at mean concentrations of about 10(2) cfu/100 ml. Mycobacteria were found in 75 and 50% of samples collected from final devices, respectively from the heated and not heated water lines. The isolates were M. gordonae (85% of isolates) and M. fortuitum (15%), but at concentrations very low. Both treatments with sodium hypochlorite (20 ppm of residual chlorine) and peracetic acid (20 ppm) resulted in the reduction of total bacterial counts and elimination of Pseudomonas from the water in the tank, but not in elimination of Pseudomonas and Legionellae from the nebulizers. The disinfectants were evidently not able to efficiently reach all the points where Pseudomonas and Legionella had settled and grown. In order to obtain total abatement it was necessary to carry out a radical restructuring of the plant, involving the replacement of the old nebulizer benches with new aerosol equipment that could be subjected to a new system of programmed thermal shock.
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PMID:[Monitoring and control of opportunistic bacteria in a spa water used for aerosol hydrotherapy]. 1635 75


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