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)

It has been reported that granulocyte/macrophage colony-stimulating factor (GM-CSF), one of the hemopoietic growth factors which regulates the function of phagocytic cells, is a potent activator of cultured macrophages and induces antimicrobial activities as well as differentiation of precursor cells. In this study, we examined the ability of recombinant murine GM-CSF to activate mouse peritoneal macrophages to restrict the growth of two different microorganisms, Candida albicans and Legionella pneumophila, both of which are important opportunistic pathogens in an immunocompromised host. Treatment of thioglycollate-elicited BDF1 mouse macrophages with GM-CSF for 24 hr enhanced the anti-C. albicans activity of the macrophages in terms of inhibiting growth of the fungi. Reactive oxygen (H2O2) and IL-1 production by the macrophages were also enhanced by treatment with GM-CSF. However, no enhancement of anti-L. pneumophila activity of macrophages obtained from either susceptible A/J or resistant BDF1 mice to L. pneumophila infection after treatment with up to 1000 units/ml GM-CSF was observed under the same conditions. When the treatment time was extended to 72 hr. GM-CSF was still unable to induce anti-L. pneumophila activity. As a control study, treatment with recombinant IFN-gamma enhanced both anti-Candida and anti-Legionella activity in cultured macrophages under the same conditions used in the GM-CSF study. Measurement of cellular iron content revealed the low iron content in IFN-gamma-treated macrophages, but no decrease of iron in GM-CSF-treated macrophages compared with the control group, indicating a possible involvement of iron as a key factor in anti-L. pneumophila activity. Thus, the results of the study show that GM-CSF activation of elicited peritoneal macrophages is selective with regard to the type of antimicrobial activity induced.
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PMID:Differential effects of granulocyte/macrophage colony-stimulating factor (GM-CSF) in enhancing macrophage resistance to Legionella pneumophila vs Candida albicans. 907 Mar 20

This study evaluated the incidence of Legionella pneumophila in dental unit water samples and investigated how the occurrence of these bacteria may be related to some physical, chemical and bacteriological characteristics of the water. The samples were taken from the incoming tap water, oral rinsing cup, air-water syringe, ultrasonic scaler, and the turbine of 23 dental units of private and public institutions. Apart from L. pneumophila (serogroup 1 and 3) isolated in 22 out of the 101 (21.8%) water samples tested, two other species were found: L. bozemanii and L. dumoffii. The highest densities and frequency of L. pneumophila were observed in the water coming into the units and in the dental units of public institutions. A negative association between L. pneumophila and 36 degrees C and 22 degrees C heterotrophic total plate counts and other gram-negative bacteria was found. An inverse association between the concentration of L. pneumophila and water temperature was also observed. The values of pH and total hardness did not show any significant difference in the L. pneumophila-positive and -negative dental unit waters. Finally, the chemical oxygen demand (COD) and residual chlorine were found to correlate positively with L. pneumophila.
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PMID:Water characteristics associated with the occurrence of Legionella pneumophila in dental units. 1070 73

This section is designed to provide a brief summary of some of the findings. A good deal of work has been conducted by Mr N. L. Pavey and the team at BSRIA, Bracknell. The BSRIA publications are an excellent source of further information. Ultraviolet radiation: UV radiation of wavelength 254 nm destroys bacteria by a mechanism of damaging nucleic acids by producing thymine dimers which disrupt DNA replication [Gavdy and Gavdy, 1980]. L. pneumophila has been reported as sensitive to UV dosages of 2,500-7,000 uW.s/cm2 [Antopol & Ellner, 1979; Knudson, 1985]. Antopol and Ellner [1979] examined the susceptibility of L. pneumophila to UV dosage. Their results indicated that 50% of the organisms were killed by 380 uWs/cm2 and 90% were killed by 920 uWs/cm2. Kills of 99 and 99.9% were obtained using 1,840 and 2,760 uWs/cm2 respectively. Muraca et al [1987] showed that continuous UV irradiation resulted in a 5 logarithm decrease in waterborne L. pneumophila in a circulating system. Gilpin [1984] reported that in laboratory buffer solutions, exposure to 1 uW of UV radiation per cm2 achieved a 50% kill of L longbeachae in 5 minutes, L. gormanii in 2-30 minutes and L pneumophila in 17 minutes. Exposure times for 99% kills for L. longbeachae, L pneumophila and L. Gormanii were 33, 48 and 63 minutes respectively. The same research worker conducted experiments using a 3 litre circulating water system, connected to a stainless steel housing containing a UV source. The UV lamp output was 7 ergs/mm2 per second per 100 cm at 254 nm. L. pneumophila was killed within 15 seconds, that is within their first pass through the system. Continuous disinfection with UV has the advantages of imparting no taste, odour or harmful chemical by-products and requires minimal operation and maintenance [Muraca et al 1988]. Keevil et al [1989] state that UV irradiation fails to clear systems of biofilm because of poor penetration into microflocs of the micro-organisms. Copper/silver ionisation: A recent study of full scale hot water test rigs incorporating copper-silver ionisation systems has been reported by Pavey, 1996. Copper and silver ions were introduced into the water by electrolysis. One of the principal mechanisms of biocidal action of these ions is thought to be cell penetration. The positively charged copper ions form electrostatic bonds with negatively charged sites on the cell wall. The cell membrane is thus distorted, allowing ingress of silver ions which attack the cell by binding at specific sites to DNA, RNA, respiratory enzymes and cellular protein, causing catastrophic failure of the life support systems of the cell. Silver and copper ion concentrations of 40 and 400 ug/L respectively were effective against planktonic Legionellae in cold water systems and hot water systems containing soft water. In hard water, the ionisation was ineffective due to the inability to control silver ion concentrations. This was caused by scaling of the electrodes and silver ion complexation by the high concentration of dissolved solids. Bosch et al [1993] had earlier extended the application of copper-silver disinfection to human enteric viruses in water, such as adenovirus, rotavirus, hepatitis A virus, and poliovirus. Their work showed that copper and silver ions in the presence of reduced levels of free chlorine did not ensure the total elimination of viral pathogens from water. In the case of an amoeba, Naegleria fowleria [responsible for primary amoebic meningoencephalitis], Cassells et al [1995] have demonstrated that a combination of silver and copper ions were ineffective at inactivating the amoebae at 80 and 800 ug/L respectively. However addition of 1.0 mg/L free chlorine produced a synergistic effect, with superior inactivation relative to either chlorine or silver-copper in isolation. A similar synergy was reported by Yahya et al [1989] in their study of Staphylococcus sp. and Pseudomonas aeruginosa. Yahya et al [1992] also suggested an additive or synergistic effect in the inactivation of coliphage MS-2 and poliovirus. Other techniques: There are a number of other techniques. We have conducted trials of most of these in the control of Legionella sp., but these fall out of the scope of this article, and as such less emphasis has been placed on them here. Ozonation: Ozone [O3] is an oxidising gas, generated electrically from oxygen [O2]. L. pneumophila can be killed at < 1 mg/L of ozone [Edelstien et al 1982]. Muraca et al [1987] found that 1-2 mg/L of continuous ozone over a six hour contact time, produced a 5 logarithm decrease of L. pneumophila. The effectiveness of ozone treatment against a range of bacteria and coliphages has been studied Botzenhart et al [1993]. E. coli was least resistant to ozone, followed by MS 2-coliphage and PhiX 174-coliphage, with L. pneumophila and Bacillus subtilis spores being the most resistant. (ABSTRACT TRUNCATED)
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PMID:Reviewing efficacy of alternative water treatment techniques. 1144 90

OBJECTIVE: To investigate the epidemiologic relatedness of nosocomial infections due to Legionella pneumophila serogroup 1 diagnosed between 1992 and 1994 in six immunocompromised patients of the same hospital and to describe the measures which were developed to control the outbreak. METHODS: Legionella strains isolated from patients and from potable hot water were compared using three typing methods: monoclonal antibody analysis, arbitrarily primed PCR and ribotyping. RESULTS: Environmental investigations revealed the presence of high levels of L. pneumophila serogroup 1 in hot water. The typing methods gave concordant results for demonstrating (1) the persistence of an epidemic strain of L. pneumophila serogroup 1 in the major water distribution circuit of the hospital over a 3-year period, and (2) the identity between patients' and environmental strains. Five of the six patients were probably infected via aerosols of hot tap water following inappropriate therapeutic procedures. Repetitive heat flushings associated with regular bacteriologic surveillance allowed correct disinfection of the water distribution systems. Specific recommendations concerning aerosol delivery and oxygen therapy were implemented in order to prevent further nosocomial legionellosis. CONCLUSIONS: The same strain of L. pneumophila had been able to colonize the main water circuit of the hospital for at least 3 years; the relatedness between clinical and environmental strains was easily confirmed by the use of molecular markers.
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PMID:Nosocomial legionellosis outbreak over a three-year period: investigation and control. 1186 53

Although the side effects of thalidomide are well known, lung toxicity has not been reported. We describe the case of a 65-year-old man with multiple myeloma (IgG kappa) in stage IA who, on the thirty-seventh day of treatment with thalidomide, developed acute coughing, general malaise, dyspnea at rest and sudoresis. Blood pressure was 90/60 mm Hg and temperature was normal. An interstitial and alveolar pattern was visible on the right side of a chest film and arterial blood gases indicated partial respiratory insufficiency (pH 7.40, PaCO2 40 mmHg, PaO2 47 mmHg). Blood analysis showed alterations expected for multiple myeloma and microbiology was negative (sputum and blood cultures and urinary antigen detection for Streptococcus pneumoniae and Legionella pneumophila). After thalidomide was withdrawn and oxygen and intravenous corticoids were administered, outcome was good. A chest film 4 days later was normal and arterial blood gases showed that respiratory insufficiency had disappeared. We conclude that severe lung toxicity should be included among the potential adverse effects of thalidomide.
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PMID:[Lung toxicity due to thalidomide]. 1279 46

Owing to the very frequent reports of Legionella's cases arising in italian hospitals we have done a microbiologic monitoring on some equipments utilized in a several ward, what represent a potential source of diffusion of germ. It has been analysed water collected from 135 bubblers for oxygen-therapy, 11 pediatric incubators and 10 dental chairs. The isolated strains ware 31 (19.23%), of which: 3 L. Pneumophila sgr. 1; 11 sgr. 3; 8 sgr. 6; 2 sgr. 7. For 6 strains identified as Legionella, have not been possible to establish sgr.
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PMID:[Unusual sources of L. pneumophila in hospital environment]. 1250 53

Legionella pneumophila is a major cause of life-threatening pneumonia, which is characterized by a high incidence of acute lung injury and resultant severe hypoxemia. Mechanical ventilation using high oxygen concentrations is often required in the treatment of patients with L. pneumophila pneumonia. Unfortunately, oxygen itself may propagate various forms of tissue damage, including acute lung injury. The effect of hyperoxia as a cofactor in the course of L. pneumophila pneumonia is poorly understood. In this study, we show that exposure to hyperoxic conditions during the evolution of pneumonia results in a marked increase in lethality in mice with Legionella pneumonia. The enhanced lethality was associated with an increase in lung permeability, but not changes in either lung bacterial burden or leukocyte accumulation. Interestingly, accelerated apoptosis as evidenced by assessment of histone-DNA fragments and caspase-3 activity were noted in the infected lungs of mice exposed to hyperoxia. TUNEL staining of infected lung sections demonstrated increased apoptosis in hyperoxic mice, predominantly in macrophages and alveolar epithelial cells. In vitro exposure of primary murine alveolar epithelial cells to Legionella in conjunction with hyperoxia accelerated apoptosis and loss of barrier function. Fas-deficient mice demonstrated partial resistance to the lethal effects of Legionella infection induced by hyperoxia, which was associated with attenuated apoptosis in the lung. These results demonstrate that hyperoxia serves as an important cofactor for the development of acute lung injury and lethality in L. pneumophila pneumonia. Exaggerated apoptosis, in part through Fas-mediated signaling, may accelerate hyperoxia-induced acute lung injury in Legionella pneumonia.
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PMID:Hyperoxia mediates acute lung injury and increased lethality in murine Legionella pneumonia: the role of apoptosis. 1268 54

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

Infection with Legionella spp. is an important cause of serious community- and hospital-acquired pneumonia, occurring sporadically and in outbreaks. Outbreaks of Legionnaires' disease have recently received considerable media attention, and some factors indicate that the problem will increase in future. Infection with Legionella spp. ranks among the three most common causes of severe pneumonia in the community setting, and is isolated in 1-40% of cases of hospital-acquired pneumonia. Underdiagnosis and underreporting are high. Only 2-10% of estimated cases are reported. Detection of a single case should not be considered an isolated sporadic event, but rather indicative of unrecognized cases. There are no clinical features unique to Legionnaires' disease; however, suspicion should be raised by epidemiologic information commensurate with the diagnosis and the presence of headache, confusion, hyponatremia, elevated creatine kinase and/or severe pneumonia. An arterial oxygen partial pressure <60mm Hg on presentation and progression of pulmonary infiltrates despite appropriate antibacterial therapy should always alert clinicians to this cause.Macrolides, fluoroquinolones and rifampin (rifampicin) are the most widely used drugs in treatment. Fluoroquinolones or azithromycin are the treatment of choice in immunosuppressed patients and those with severe pneumonia. Incorporation of the legionella urinary antigen test in emergency departments in hospitals and progressive improvement in this test will, in the near future, permit appropriate diagnosis and treatment of this frequent, sometimes severe, illness.
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PMID:Legionnaires' disease: update on epidemiology and management options. 1472 5

Among the main characteristics of Legionella pneumophila pneumonia are acute lung injury and severe hypoxemia. Although high oxygen supplementation is a valuable supportive therapy in these patients, oxygen itself is known to be a risk factor for acute lung injury. The effects of hyperoxia on lung injury of mice with Legionella pneumonia were examined. Hyperoxia treatment reduced survival of the infected mice in an oxygen concentration- and exposure time-dependent manner. The enhanced lethality was associated with an increase in total lung weight and apoptosis markers, but not with bacterial burden in the lungs. Hyperoxia decreased the levels of the antioxidant glutathione (GSH) in infected lungs. Exogenous tumour necrosis factor-alpha (TNF-alpha) improved the survival of infected mice kept under hyperoxia. TNF-alpha effects were associated with restoration of total lung weight and histone DNA and GSH levels on day 2, whereas the lung bacterial burden did not differ significantly. Moreover, upregulation of GSH by TNF-alpha was observed in the lungs of mice without infection. These results demonstrate that hyperoxia exacerbates L. pneumophila pneumonia. The data suggest that TNF-alpha may be a potential therapeutic candidate for these individuals, not only through modulating host antibacterial systems, but also by mediating induction of the antioxidant GSH.
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PMID:Legionella-induced acute lung injury in the setting of hyperoxia: protective role of tumour necrosis factor-alpha. 1527 58


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