Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strains of Pseudomonas aeruginosa from patients with cystic fibrosis (CF) are unusual. The majority have a rough lipopolysaccharide (LPS) which renders them nontypeable by conventional typing systems based on a serological reaction with the O polysaccharide of smooth LPS. We developed a new typing scheme using a pilin gene probe as a marker for hybridization with endonuclease-digested genomic DNA from P. aeruginosa. Twenty-one different restriction fragment length polymorphism (RFLP) types were found among 249 isolates. RFLP type 7 was recovered only from patients with thermal burns (9 of 14 isolates) in both Vancouver, British Columbia, and Edmonton, Alberta, Canada. None of the other RFLP types showed a clear predilection for disease state or environmental niche. Multiple morphologically different isolates from individual patients with CF were studied; each isolate in 33 of 40 sputum samples had an identical RFLP type, despite considerable LPS serotype heterogeneity. Sequential isolates from 23 patients were studied; in 10 isolates there was a clear change in both the RFLP and the LPS serotype. We conclude that patients with CF usually harbor a single P. aeruginosa RFLP type in their sputa, but that one strain can replace another as the predominant colonizing type.
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PMID:Use of a pilin gene probe to study molecular epidemiology of Pseudomonas aeruginosa. 257 4

The mechanism of chloramphenicol resistance was examined in a high-level-resistant isolate of Pseudomonas cepacia from a patient with cystic fibrosis. We investigated potential resistance mechanisms, including production of chloramphenicol acetyltransferase, ribosomal resistance, and decreased permeability. This strain (MIC, 200 micrograms/ml) had no detectable chloramphenicol acetyltransferase activity. In in vitro translation experiments in which we compared the resistant isolate with a susceptible strain of P. cepacia, inhibition of amino acid incorporation was equivalent even in organisms that were preincubated with sub-MICs of chloramphenicol. A 21.9-kilobase (kb) fragment of DNA was cloned which coded for chloramphenicol resistance; this fragment was expressed in P. cepacia but not in Escherichia coli. Quantitation of chloramphenicol uptake in the isogenic pair of susceptible and resistant organisms revealed a nearly 10-fold decrease of drug entry into the resistant strain. Comparison of isolated outer membrane proteins and lipopolysaccharide patterns identified no significant differences between the isogenic pair of organisms. We concluded that the mechanism of chloramphenicol resistance in this strain is decreased permeability.
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PMID:Chloramphenicol resistance in Pseudomonas cepacia because of decreased permeability. 271 57

Since beta-lactam resistance is a feature of Pseudomonas cepacia isolates causing pulmonary infections in cystic fibrosis (CF), this study was undertaken to determine whether alterations in beta-lactam permeability mediate drug resistance in this species. A beta-lactam-susceptible non-CF isolate (strain 75-26), a resistant mutant derived from 75-26 by selection for cross-resistance to ciprofloxacin and ceftazidime, and two resistant CF isolates of P. cepacia were used. Permeability constants were calculated from the rate of nitrocefin hydrolysis in intact bacterial cells. Qualitative changes in outer membrane proteins were determined electrophoretically. The permeability constants of the mutant and the resistant CF isolates were lower than the value for the reference strain, 75-26. Whereas the lipopolysaccharide side chains were present in the test and reference strains, the resistant mutant and the CF isolates contained reduced amounts of the 36-kilodalton (kDa) outer membrane protein and failed to express the 27-kDa outer membrane protein. These observations suggest that the 27-kDa outer membrane protein may be a major porin or a major protein component of the porin complex in P. cepacia and that decreased expression of the 36-kDa outer membrane and loss of the 27-kDa porin are associated with high-level beta-lactam resistance in some CF isolates of P. cepacia.
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PMID:Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates. 285 96

We tested nonmucoid Pseudomonas aeruginosa isolates obtained from cystic fibrosis (CF) patients for the expression of lipopolysaccharide (LPS) serotype antigens, serum sensitivity, and production of mucoid exopolysaccharide (MEP). When all nonmucoid isolates were compared with a set of random mucoid isolates, 20 of 52 (38%) nonmucoid isolates were typable and serum resistant, compared with 13 of 51 (24%) mucoid isolates (P = 0.16 by chi-square analysis). However, nonmucoid strains from CF patients colonized only with nonmucoid strains were more frequently typable and serum resistant (67%) than were nonmucoid isolates from patients cocolonized with mucoid strains (31%) (P = 0.012, Fisher exact test). An inhibition enzyme-linked immunosorbent assay done with bacterial extracts, a direct-whole-cell enzyme-linked immunosorbent assay done with affinity-purified antibody to MEP, and immune electron microscopy all demonstrated production of MEP by all nonmucoid P. aeruginosa isolates tested, including nonmucoid revertants of mucoid strains. No other bacterial species tested positive in these assays. These findings suggest that MEP is produced by all P. aeruginosa isolates obtained from CF patients, that the initial colonizing nonmucoid strains produce a smooth LPS, and that once LPS-rough, mucoid strains appear in the sputum, the predominant LPS phenotype is rough regardless of colony morphology.
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PMID:Polysaccharide surface antigens expressed by nonmucoid isolates of Pseudomonas aeruginosa from cystic fibrosis patients. 294 59

Pseudomonas aeruginosa is a gram-negative pathogen, versatile and opportunistic in terms of its genetics, metabolic potential, and mechanisms of virulence. This versatility enables it to respond to variable and frequently adverse environmental conditions. Considered by many to be an aerobic organism, it is capable of growing anaerobically if certain substrates are available, for example, nitrates or arginine. Diversity of mechanisms of genetic exchange, including transformation, transduction, and conjugation, help P. aeruginosa adapt to changing conditions by acquiring new genetic information. Genetic manipulations have been exploited in recent years to study the basic biology of this bacterial species and the roles of its numerous virulence factors. Recently, transposon mutagenesis techniques and recombinant DNA methods (cloning) have been used to study some of the virulence factors of P. aeruginosa. The pathogenesis of P. aeruginosa infections is multifactorial, as manifested by the numerous toxins, or virulence factors, it produces and the variety of diseases it causes. P. aeruginosa is invasive and toxigenic. Infections appear to occur in stages: bacterial adherence, colonization, invasion and dissemination, and systemic or toxemic disease. Virulence factors can contribute to one or several stages of pathogenesis. Surface factors, including pili, lipopolysaccharide, and polysaccharide slime (alginate), probably contribute to the first two stages. Polysaccharide slime and lipopolysaccharide may also contribute to other processes later in the course of infection. Toxins, including exotoxin A and phospholipase C (hemolysin), and proteases of P. aeruginosa may contribute to tissue damage and dissemination. They may also aid in the procurement of nutrients required by the bacteria in the early stages of infection. The significance of the different virulence factors probably depends on the infection. Alginate production and phospholipase C are likely to have special significance in respiratory infections, particularly in cystic fibrosis.
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PMID:Pseudomonas aeruginosa: biology, mechanisms of virulence, epidemiology. 300 72

Pulmonary macrophage phagocytosis of Pseudomonas aeruginosa is defective when this pathogen is opsonized with IgG antibodies isolated from serum samples from patients with cystic fibrosis (CF). To evaluate this defect further, IgG subclasses in the serum and lung fluids of patients with CF were quantitated. The pattern of IgG subclasses in serum specimens from patients with CF (n = 15) and in patients without CF but with chronic obstructive airway disease and recurrent P. aeruginosa infection (n = 4) was significantly altered from that found in normal subjects (n = 31). Immunoglobulin-G2 and IgG3 expressed as percentages of total IgG subclasses or in micrograms per milliliter of serum were significantly elevated in the serum specimens of these patients (p less than 0.05), and IgG1 was significantly decreased (p less than 0.01). It appears that the increase in IgG2 in the serum of patients with CF and those without CF but with chronic P. aeruginosa infection may be in response to chronic antigenic stimulation by P. aeruginosa lipopolysaccharide. Evidence presented to support this includes: (1) IgG2 is not increased in CF serum if a history of P. aeruginosa infection is absent, (2) IgG2 levels expressed as percentages of total IgG subclasses in CF lung fluids were positively correlated (r = 0.73) with the number of colony-forming units of P. aeruginosa present in CF sputum specimens, and (3) IgG antibodies specifically eluted from P. aeruginosa lipopolysaccharide ligands on affinity gels were largely restricted to IgG2. The opsonic index, ([IgG3] + [IgG1]) divided by ([IgG2] + [IgG4]), is inverted in CF lung fluids (0.73:1; normal, 2:1). Because pulmonary macrophages show surface receptors binding primarily with IgG3 and IgG1, it may be that such an alteration in IgG subclasses in the respiratory secretions of patients with CF further inhibits opsonin-mediated clearance of P. aeruginosa.
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PMID:Immunoglobulin-G subclasses in cystic fibrosis. IgG2 response to Pseudomonas aeruginosa lipopolysaccharide. 308 64

Serum from cystic fibrosis patients colonized with Pseudomonas aeruginosa specifically inhibits phagocytosis of P. aeruginosa by alveolar macrophages. Serum was examined for P. aeruginosa lipopolysaccharide-specific immunoglobulin G (IgG) subclass levels (by enzyme-linked immunosorbent assay) and for the effect on macrophage phagocytosis (by radiolabeled P. aeruginosa uptake). Sera from cystic fibrosis patients with no known P. aeruginosa colonization history had negligible amounts of lipopolysaccharide-specific IgG and a mean phagocytic enhancement of 5%. The sera of normal volunteers also had negligible amounts of lipopolysaccharide-specific IgG. Serum from cystic fibrosis patients with P. aeruginosa respiratory tract infections had substantial titers (range, 1:20 to 1:1,280) of lipopolysaccharide-specific IgG2, IgG3, and IgG4 and a mean phagocytic inhibition of 56%. However, these patients had low or absent titers of lipopolysaccharide-specific IgG1. No consistent variation in the level of individual IgG subclasses in the sera of colonized patients was observed, as determined by radial immunodiffusion. The results suggest that during P. aeruginosa infection phagocytosis-inhibitory activity develops coincident with production of lipopolysaccharide-specific IgG subclasses.
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PMID:Association with phagocytic inhibition of anti-Pseudomonas aeruginosa immunoglobulin G antibody subclass levels in serum from patients with cystic fibrosis. 308 22

The relevance of circulating immune complexes, plasma complement activation, and serum antibodies against discrete antigens of Pseudomonas aeruginosa, to the clinical course in patients with cystic fibrosis (CF) is unknown. We related these factors to outcome in 49 patients with CF colonized by P. aeruginosa, comparing 14 who died of lung disease with 35 survivors of similar age and duration of colonization, as well as 9 uncolonized patients with CF, 24 patients with other bronchorrheic lung disease, and 10 healthy control subjects. The patients with CF colonized by P. aeruginosa who died had a higher incidence of immune complexes than did survivors (71 versus 40%, p less than 0.05). Moreover, C4 activation was highly associated with immune complexes and mortality (p less than 0.001 for each). Those who died also had much higher levels of IgG antibodies to P. aeruginosa lipopolysaccharide (LPS) and exotoxin A than did survivors colonized by P. aeruginosa (p less than 0.005 and p = 0.01, respectively), whereas both groups had similar levels of P. aeruginosa sonicate, elastase, alkaline protease, and endotoxin core antibodies. We conclude that increasing levels of serum IgG antibodies to P. aeruginosa LPS and exotoxin A and the presence of systemic immune complexes and complement activation are associated with poor prognosis in CF, and may provide useful noninvasive markers for studying the possible immunopathogenesis of CF lung disease.
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PMID:Association of systemic immune complexes, complement activation, and antibodies to Pseudomonas aeruginosa lipopolysaccharide and exotoxin A with mortality in cystic fibrosis. 308 45

Production of both alginic acid and lipopolysaccharide by a mucoid strain of Pseudomonas aeruginosa, SRM-3, was studied in a chemostat system during growth under nutrient-limiting conditions chosen to reflect the chronic growth conditions in the lungs of cystic fibrosis patients. Since mucoid strains have been shown to elaborate extracellular proteases and phospholipase C, nitrogen and phosphate limitation were selected for analysis. A modified alginate-promoting medium containing either 1 mM glutamate or 0.05 mM K2HPO4 as limiting nutrient and doubling times of 1.6 to 15.7 h were used. Under nitrogen limitation, strain SRM-3 produced 1.4 mg of uronic acid per mg (dry weight) of cells at all doubling times studied. However, phosphate limitation resulted in the synthesis of only 0.4 mg of uronic acid per mg (dry weight) of cells. The role of phosphate in alginic acid polysaccharide production was further investigated by using phosphorylcholine, a product of phospholipase C activity on phosphatidylcholine, the major lung surfactant. No only were mucoid cells capable of utilizing phosphorylcholine for growth, but a highly specific interaction occurred among phosphorylcholine, alginate, and whole cells, resulting in greatly enhanced culture viscosity. Electron micrographs showed the gradual formation of a capsule during growth on phosphorylcholine, indicating that the mucoid strain has the ability to utilize surfactant not only as a nutrient source but also for constructing a capsule with greatly enhanced adhesive properties.
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PMID:Phosphorylcholine stimulates capsule formation of phosphate-limited mucoid Pseudomonas aeruginosa. 312 46

Human IgG response to Pseudomonas aeruginosa core lipopolysaccharide determinants was measured after both acute and chronic pseudomonas infection by using lipopolysaccharide purified from PAC605 cells (the most lipopolysaccharide-defective or "roughest" mutant of P. aeruginosa yet described) as a solid phase antigen in ELISA and Western blot immunoassay. The geometric mean IgG anti-PAC605 lipopolysaccharide titer of sera from 18 cystic fibrosis (CF) patients with chronic pseudomonas pulmonary infection was 1808, compared to 171 for convalescent sera of 10 patients with acute pseudomonas bacteremia (p less than 0.001) and 211 for 5 normal human volunteers (p less than 0.001). Western blot immunoassay demonstrated specific IgG anti-core antibodies in 11/18 sera from CF patients but not in the sera of the convalescent bacteremic patients or normal volunteers. IgG anti-Pseudomonas core lipopolysaccharide antibodies appear to be a marker of chronic infection; the possible protective role of these antibodies remains to be established.
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PMID:Human IgG antibodies to Pseudomonas aeruginosa core lipopolysaccharide determinants are detected in chronic but not acute pseudomonas infection. 312 49


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