Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhodococcus equi, an intracellular organism causing pneumonia and lung abscesses in foals, is generally thought to be non-haemolytic. In the present study, however, 13 of 14 representative isolates were found to be haemolytic when tested on agar media containing washed red blood cells rather than whole blood. Red cells of rabbits, dogs, horses and man were more sensitive to lysis than were those of ruminants. Two new enzymatic activities of the species were defined: a lecithinase and a phosphatidylinositol-specific phospholipase C (PI-PLC). As judged from tests for trypsin, temperature and ethanol sensitivity, the haemolytic activity was primarily dependent on PI-PLC though the participation of lecithinase seemed probable. The haemolytic activity of growing strains, but not of cell-free preparations, was partially inhibited by lecithin but enhanced by cholesterol; however, cholesterol oxidase (CO) activity, known to mediate cooperative lysis of RBC sensitized with sphingomyelin-specific phospholipases C or D of some other species, did not contribute to the direct haemolysis caused by R. equi as demonstrated here.
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PMID:Haemolytic and phospholipase C (PLC) activities of Rhodococcus equi. 798 59

We developed an experimental model of acute Pseudomonas aeruginosa pneumonia in anesthetized ventilated rabbits to determine whether bacterial-induced injury to the alveolar epithelium would occur and the effect of the injury on the pleural space. Dose-response studies established that 10(9) colony-forming units of P. aeruginosa (wild-type strain, PAO-1) were required to injure the epithelial barrier and to cause pleural empyema with exudative pleural effusions that contained both the instilled alveolar protein tracer and P. aeruginosa. We explored the mechanisms of P. aeruginosa-induced lung and pleural injury by using three isogenic bacterial strains to compare several extracellular virulence products. PAO-S21, which carries an insertion mutation in a regulatory gene that prevents the production of exoenzyme S, resulted in no lung or pleural injury. PAO-R1, which carries a deletion in a regulatory gene that controls the production of elastase and alkaline protease, caused the same degree of lung and pleural injury as PAO-1 did. Instillation of PLC-SRN, which has both structural genes encoding phospholipase C activity deleted, resulted in a moderate reduction in alveolar epithelial injury. Although other products may be involved, exoenzyme S and phospholipase C are important in mediating injury to the alveolar epithelial barrier in acute P. aeruginosa pneumonia in rabbits.
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PMID:Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits. 828 18

A 14-month-old boy presented with generalised vesicular eruption involving the face, trunk and extremities accompanied by high grade fever. He had associated redness and purulent discharge from both eyes. Examination revealed erosions on the tongue, soft palate and genitalia with haemorrhagic crusts on the lips and nasal orifices. All laboratory investigations were within normal limits except leucocytosis. Chest x-ray showed left middle zone pneumonitis. Treatment was by paracetamol, antibiotics and oral acyclovir. Desquamation started from the eighth day. Our purpose in reporting this case is to highlight the fact that varicella can be atypical with distal involvement and can present as SJS-TEN overlap syndrome.
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PMID:Atypical varicella zoster as SJS-TEN overlap syndrome with involvement of palm and sole. 1682 98

Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C-gamma2 (PLC-gamma2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-gamma2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav.
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PMID:Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCgamma2 signaling axis in mice. 1793 69

Pseudomonas aeruginosa is a gram-negative bacterium that causes chronic infection in cystic fibrosis patients. We reported recently that P. aeruginosa modulates epithelial Na(+) channel (ENaC) expression in experimental chronic pneumonia models. For this reason, we tested whether LPS from P. aeruginosa alters ENaC expression and activity in alveolar epithelial cells. We found that LPS induces a approximately 60% decrease of ENaC apical current without significant changes in intracellular ENaC or surface protein expression. Because a growing body of evidence reports a key role for extracellular nucleotides in regulation of ion channels, we evaluated the possibility that modulation of ENaC activity by LPS involves extracellular ATP signaling. We found that alveolar epithelial cells release ATP upon LPS stimulation and that pretreatment with suramin, a P2Y(2) purinergic receptor antagonist, inhibited the effect of LPS on ENaC. Furthermore, ET-18-OCH3, a PLC inhibitor, and Go-6976, a PKC inhibitor, were able to partially prevent ENaC inhibition by LPS, suggesting that the actions of LPS on ENaC current were mediated, in part, by the PKC and PLC pathways. Together, these findings demonstrate an important role of extracellular ATP signaling in the response of epithelial cells to LPS.
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PMID:Modulation of epithelial sodium channel activity by lipopolysaccharide in alveolar type II cells: involvement of purinergic signaling. 2000 15

Mycoplasma pneumoniae causes up to 10-40 % of community-acquired pneumonias. The incidence of M. pneumoniae pneumonia is greatest among children and young adults. The symptoms of M. pneumoniae upper and lower respiratory infections are usually mild and often self-limited. The most frequent extrapulmonary complications present in CNS, heart and skin. The skin affiliations are usually transient erythematous maculopapular or vesicular rashes but may sometimes evolve into Stevens-Johnson syndrome. M. pneumoniae is one of the most common microbe behind the infectious causes of SJS. We present a patient who developed incomplete Stevens-Johnson syndrome concomitant of Mycoplasma pneumoniae pneumonia.
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PMID:[Mycoplasma pneumoniae and Stevens-Johnson syndrome]. 2321 Feb 90

Legionella pneumophila is a water-borne bacterium that causes pneumonia in humans. PlcA and PlcB are two previously defined L. pneumophila proteins with homology to the phosphatidylcholine-specific phospholipase C (PC-PLC) of Pseudomonas fluorescens. Additionally, we found that Lpg0012 shows similarity to PLCs and has been shown to be a Dot/Icm-injected effector, CegC1, which is designated here as PlcC. It remained unclear, however, whether these L. pneumophila proteins exhibit PLC activity. PlcC expressed in Escherichia coli hydrolyzed a broad phospholipid spectrum, including PC, phosphatidylglycerol (PG), and phosphatidylinositol. The addition of Zn(2+) ions activated, whereas EDTA inhibited, PlcC-derived PLC activity. Protein homology search revealed that the three Legionella enzymes and P. fluorescens PC-PLC share conserved domains also present in uncharacterized fungal proteins. Fifteen conserved amino acids were essential for enzyme activity as identified via PlcC mutagenesis. Analysis of defined L. pneumophila knock-out mutants indicated Lsp-dependent export of PG-hydrolyzing PLC activity. PlcA and PlcB exhibited PG-specific activity and contain a predicted Sec signal sequence. In line with the reported requirement of host cell contact for Dot/Icm-dependent effector translocation, PlcC showed cell-associated PC-specific PLC activity after bacterial growth in broth. A PLC triple mutant, but not single or double mutants, exhibited reduced host killing in a Galleria mellonella infection model, highlighting the importance of the three PLCs in pathogenesis. In summary, we describe here a novel Zn(2+)-dependent PLC family present in Legionella, Pseudomonas, and fungi with broad substrate preference and function in virulence.
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PMID:The Legionella pneumophila Dot/Icm-secreted effector PlcC/CegC1 together with PlcA and PlcB promotes virulence and belongs to a novel zinc metallophospholipase C family present in bacteria and fungi. 2345 99

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that causes a wide range of infections including pneumonia, septicemia, necrotizing fasciitis and severe wound and urinary tract infections. Analysis of A. baumannii representative strains grown in Chelex 100-treated medium for hemolytic activity demonstrated that this pathogen is increasingly hemolytic to sheep, human and horse erythrocytes, which interestingly contain increasing amounts of phosphatidylcholine in their membranes. Bioinformatic, genetic and functional analyses of 19 A. baumannii isolates showed that the genomes of each strain contained two phosphatidylcholine-specific phospholipase C (PC-PLC) genes, which were named plc1 and plc2. Accordingly, all of these strains were significantly hemolytic to horse erythrocytes and their culture supernatants tested positive for PC-PLC activity. Further analyses showed that the transcriptional expression of plc1 and plc2 and the production of phospholipase and thus hemolytic activity increased when bacteria were cultured under iron-chelation as compared to iron-rich conditions. Testing of the A. baumannii ATCC 19606T plc1::aph-FRT and plc2::aph isogenic insertion derivatives showed that these mutants had a significantly reduced PC-PLC activity as compared to the parental strain, while testing of plc1::ermAM/plc2::aph demonstrated that this double PC-PLC isogenic mutant expressed significantly reduced cytolytic and hemolytic activity. Interestingly, only plc1 was shown to contribute significantly to A. baumannii virulence using the Galleria mellonella infection model. Taken together, our data demonstrate that both PLC1 and PLC2, which have diverged from a common ancestor, play a concerted role in hemolytic and cytolytic activities; although PLC1 seems to play a more critical role in the virulence of A. baumannii when tested in an invertebrate model. These activities would provide access to intracellular iron stores this pathogen could use during growth in the infected host.
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PMID:Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and Virulence of Acinetobacter baumannii. 2787 72

Staphylococcus aureus is frequently isolated from patients with community-acquired pneumonia and acute respiratory distress syndrome (ARDS). ARDS is associated with staphylococcal phosphatidylinositol-specific phospholipase C (PI-PLC); however, the role of PI-PLC in the pathogenesis and progression of ARDS remains unknown. Here, we showed that recombinant staphylococcal PI-PLC possesses enzyme activity that causes shedding of glycosylphosphatidylinositol-anchored CD55 and CD59 from human umbilical vein endothelial cell surfaces and triggers cell lysis via complement activity. Intranasal infection with PI-PLC-positive S. aureus resulted in greater neutrophil infiltration and increased pulmonary oedema compared with a plc-isogenic mutant. Although indistinguishable proinflammatory genes were induced, the wild-type strain activated higher levels of C5a in lung tissue accompanied by elevated albumin instillation and increased lactate dehydrogenase release in bronchoalveolar lavage fluid compared with the plc- mutant. Following treatment with cobra venom factor to deplete complement, the wild-type strain with PI-PLC showed a reduced ability to trigger pulmonary permeability and tissue damage. PI-PLC-positive S. aureus induced the formation of membrane attack complex, mainly on type II pneumocytes, and reduced the level of CD55/CD59, indicating the importance of complement regulation in pulmonary injury. In conclusion, S. aureus PI-PLC sensitised tissue to complement activation leading to more severe tissue damage, increased pulmonary oedema, and ARDS progression.
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PMID:Staphylococcal phosphatidylinositol-specific phospholipase C potentiates lung injury via complement sensitisation. 3129 Feb 10