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At least 595 records · Page 33Linked to original sources
PubMed1993

Kinetics of serum and ocular antibody responses in susceptible mice that received a secondary corneal infection with Pseudomonas aeruginosa.

When susceptible C57BL/6J mice were infected with Pseudomonas aeruginosa in one eye and then reinfected in the previously uninfected contralateral control eye either 4 or 8 weeks after the primary infection, approximately 20 to 30% of the mice receiving a 4-week reinfection regimen restored corneal clarity within 4 weeks, while almost all of the 8-week-reinfected mice restored corneal clarity within 3 to 6 days postinfection. However, the rate of bacterial clearance was the same in both sets of mice despite the presence of opsonophagocytic antibodies only in the 8-week-reinfected mice. As determined by enzyme-linked immunosorbent assay, immunoglobulin G was the major immunoglobulin in both serum and ocular tissue of both mouse sets, and the immunoglobulin G level was two- to fourfold higher after the 8-week secondary infection than in the 4-week-reinfected mice.

Animals↗
PubMed2003

A translocated protein tyrosine phosphatase of Pseudomonas syringae pv. tomato DC3000 modulates plant defence response to infection.

Pseudomonas syringae strains translocate effector proteins into host cells via the hrp-encoded type III protein secretion system (TTSS) to facilitate pathogenesis in susceptible plants. However, the mechanisms by which pathogenesis is favoured by these effectors are not well understood. Individual strains express multiple effectors with apparently distinct activities that are co-ordinately regulated by the alternative sigma factor HrpL. Genes for several effectors were identified in the P. syringae pv. tomato DC3000 genome using a promoter trap assay to identify HrpL-dependent promoters. In addition to orthologues of avrPphE and hrpW, an unusual allele of avrPphD was detected that carried an IS52 insertion. Using this avrPphD::IS52 allele as a probe, a wild-type allele of avrPphD, hopPtoD1, and a chimeric homologue were identified in the DC3000 genome. This chimeric homologue, identified as HopPtoD2 in the annotated DC3000 genome, consisted of an amino terminal secretion domain similar to that of AvrPphD fused to a potential protein tyrosine phosphatase domain. Culture filtrates of strains expressing HopPtoD2 were able to dephosphorylate pNPP and two phosphotyrosine peptides. HopPtoD2 was shown to be translocated into Arabidopsis thaliana cells via the hrp-encoded TTSS. A DeltahopPtoD2 mutant of DC3000 exhibited strongly reduced virulence in Arabidopsis thaliana. Ectopic expression of hopPtoD2 in P. syringae Psy61 that lacks a native hopPtoD2 orthologue delayed the development of several defence-associated responses including programmed cell death, active oxygen production and transcription of the pathogenesis-related gene PR1. The results indicate that HopPtoD2 is a translocated effector with protein tyrosine phosphatase activity that modulates plant defence responses.

Arabidopsis↗
PubMed1975

Protective properties and haemagglutinins in serum from humans and in serum from mice injected with a new polyvalent Pseudomonas vaccine.

Mice given single injections of a polyvalent pseudomonas vaccine produced anti-pseudomonas haemagglutinins against the 16 component immunogens of the multivalent vaccine. Mice passively immunized with sera from vaccinated mice were protected against lethal challenge by 8/10 strains of Ps. aeruginosa of homologous serotype. Protection by the serum was inversely proportional to the virulence of the challenge strains. Anti-pseudomonas haemagglutinins were always present in sera which passively protected mice against pseudomonas infection. Low levels of anti-pseudomonas haemagglutinins were present in some sera which failed to passively immunize mice against pseudomonas infection. Anti-pseudomonas haemagglutinins and antibodies involved in passive protection were mainly in the IgM fractions of mouse serum. Control human sera contained anti-pseudomonas haemagglutinins against most serotypes of Ps. aeruginosa. Sera from patients with burns contained high levels of anti-pseudomonas haemagglutinins against some but not all serotypes of Ps. aeruginosa. Sera from both controls and patients with burns passively protected mice against pseudomonas infection.

Agglutinins↗
PubMed1976

Murine gastrointestinal tract as a portal of entry in experimental Pseudomonas aeruginosa infections.

Peroral administration of viable Pseudomonas aeruginosa into the stomach of mice resulted in an acute systemic infection, with death occurring within 72 h. One strain, ATCC 19660, a non-encapsulated form of P. aeruginosa, had a median lethal dose of 5.3 X 10(6) colony-forming units, whereas two encapsulated strains, ATCC 17933 and 17934, had median lethal dose values of 5.0 x 10(7) and 5.6 x 10(7) colony-forming units, respectively. Each strain required fewer organisms to establish a lethal infection via the stomach than by intravenous or intraperitoneal routes. The non-encapsulated strain, ATCC 19660, did not cause any diarrhea in the infected animals, whereas the two encapsulated strains, although less virulent, caused diarrhea when administered perorally. No signs of necrosis were noted within the gastrointestinal tract; however, hematogenous spread of the organism resulted in a vasculitis associated with the pulmonary vessels and bacterial invasion of the renal tissues. Treatment of animals with antineoplastic drugs 24 h before or simultaneously with peroral challenge resulted in an increased susceptibility to infection.

Administration, Oral↗
PubMed2005

Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.

The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated. P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology and cytokine production were used as indicators. The garlic treatment initially provoked a higher degree of inflammation, and significantly improved clearing of the infecting bacteria. The results indicate that a QS-inhibitory extract of garlic renders P. aeruginosa sensitive to tobramycin, respiratory burst and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections.

Animals↗
PubMed2005

Cystic fibrosis lung disease following infection with Pseudomonas aeruginosa in Cftr knockout mice using novel non-invasive direct pulmonary infection technique.

To better understand the mechanism of lung infection with Pseudomonas aeruginosa (P. aeruginosa), many techniques have been developed in order to establish lung infection in rodents. A model of chronic lung infection, using tracheotomy to inoculate the bacteria, has been extensively used in the cystic fibrosis (CF) mouse model of lung infection. The cystic fibrosis transmembrane channel (Cftr) knockout (KO) mice are smaller than normal mice and are more sensitive to housing and nutritional conditions, leading to small amounts of animals being available for experiments. Because of these characteristics, and because of the invasiveness of the infection procedure which we, and others, have been using to mimic the lung infection, we sought to find an alternative way to study the inflammatory response during lung P. aeruginosa infection. The technique we describe here consists of the injection of bacterial beads directly into the lungs through the mouth without the need of any tracheal incisions. This technique of direct pulmonary delivery enables much faster infection of the animals compared with the intratracheal technique previously used. The use of this less invasive technique allows the exclusion of the surgery-related inflammation. Our results show that, using the direct pulmonary delivery technique, the KO mice were more susceptible to P. aeruginosa lung infection compared with their wild-type (WT) controls, as shown by their increased weight loss, higher bacterial burden and more elevated polymorphonuclear (PMN) alveolar cell recruitment into the lungs. These differences are consistent with the pathological profiles observed in CF patients infected with P. aeruginosa. Overall, this method simplifies the infection procedure in terms of its duration and invasiveness, and improves the survival rate of the KO mice when compared with the previously used intratracheal procedure.

Analysis of Variance↗
PubMed2004

Recombinant OprF-OprI as a vaccine against Pseudomonas aeruginosa infections.

A vaccine against Pseudomonas aeruginosa based on recombinant outer membranes has been developed. After intramuscularly injecting into patients with severe burns, antibodies against P. aeruginosa were induced. Vaccination was well tolerated. Intranasal application of the vaccine into volunteers, induced specific s-IgA antibodies. We conclude that the newly developed vaccine may be suitable for protection of the main risk groups of P. aeruginosa infections. In particular, for the protection of burn patients and patients with cystic fibrosis.

Administration, Intranasal↗
PubMed1986

[Antibiotic therapy of Pseudomonas aeruginosa infections].

Antibiotics active against Pseudomonas aeruginosa are carboxy- and ureidopenicillins, some cephalosporins, aztreonam, imipenem, aminoglycosides, fluoroquinolones and, in some special circumstances, polymyxins and fosfomycin. The choice of the antibiotic should be based not only on minimal inhibitory concentrations in vitro, but also on the inoculum effect, on the speed with which bacteria are killed, on natural or acquired resistance and on data obtained from experimental infections in animals. Antibiotics used against P. aeruginosa infections must be rapidly bactericidal. Since the prognosis is severe, the initial treatment given before the sensitivity of the strain is known must combine a beta-lactam antibiotic and an aminoglycoside, both being selected among the most regularly active.

Anti-Bacterial Agents↗
PubMed1996

Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group.

To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).

Antibodies, Bacterial↗
PubMed1990

Therapeutic efficacy of granulocyte colony-stimulating factor alone and in combination with antibiotics against Pseudomonas aeruginosa infections in mice.

The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed. Bacterial growth in the infected thigh muscle was suppressed by G-CSF treatment. The change in the number of peripheral blood polymorphonuclear leukocytes (PMN) after bacterial challenge was investigated. The results showed that G-CSF could stimulate stronger defense mechanisms after stimulation by bacterial challenge. In the G-CSF-treated group, more clusters of matured PMN were observed in the infected thigh muscle 6 h after bacterial challenge. Next, the correlation between the number of PMN in the blood at the time of infection and the therapeutic efficacy of antibiotics was investigated. The therapeutic efficacy of ceftazidime, a beta-lactam antibiotic, was affected by the number of blood PMN at the time of infection. In particular, a decrease of peripheral blood PMN at the time of infection resulted in a dramatic decrease in the efficacy of ceftazidime. The reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.

Animals↗
PubMed1987

Analysis of continuous ambulatory peritoneal dialysis-related Pseudomonas aeruginosa infections.

The outcomes of all continuous ambulatory peritoneal dialysis-related infections due to Pseudomonas aeruginosa (n = 33) were analyzed and compared with the outcomes of infections due to all other microorganisms (n = 663) over a seven-year period. There were 16 catheter infections (exit site or tunnel infection or both), seven episodes of peritonitis, and 10 episodes of catheter infections associated with peritonitis due to P. aeruginosa. Catheters were removed in 58 percent (19 of 33) of the infections due to P. aeruginosa, but in only 16 percent (104 of 663) of the infections due to other organisms (p less than 0.01). All P. aeruginosa catheter infections associated with P. aeruginosa peritonitis resulted in catheter loss. P. aeruginosa catheter infections not associated with peritonitis also often did not resolve with antibiotic therapy (nine of 16 or 56 percent of catheters removed compared with 42 of 317 or 13 percent of catheters removed for other organisms, p less than 0.01). However, P. aeruginosa peritonitis episodes that were not associated with a catheter infection were no more likely to result in catheter loss than were peritonitis episodes due to other organisms (one of seven compared with 37 of 256, 14 percent for both). It is concluded that catheter infections due to P. aeruginosa with or without associated peritonitis usually require catheter removal. Conversely, P. aeruginosa peritonitis without a catheter infection often does not require catheter removal.

Aminoglycosides↗
PubMed2003

Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection.

Pseudomonas aeruginosa is an opportunistic respiratory pathogen that accounts for most of the morbidity and mortality in cystic fibrosis (CF) patients. In CF-affected lungs, the bacteria undergo conversion from a non-mucoid to a non-tractable mucoid phenotype, due to overproduction of alginate. The effect of alginate production on pathogenicity was investigated by using an acute lung infection mouse model that compared a non-mucoid P. aeruginosa strain, PAO1, to its constitutive alginate-overproducing derivative, Alg(+) PAOmucA22, and an alginate-defective strain, Alg(-) PAOalgD. Bacterial suspensions were instilled into the left bronchus and examined 24 and 48 h post-infection. The highest bacterial loads and the most severe lung pathology were observed with strain Alg(-) PAOalgD at 24 h post-infection, which may have been due to an increase in expression of bacterial elastase by the mutant. Significantly lower lung and spleen bacterial loads were found in the two non-mucoid (PAO1 and Alg(-) PAOalgD) groups, compared to the mucoid Alg(+) PAOmucA22 group, between 24 and 48 h post-infection. The positive correlation between lung bacteriology and lung macroscopic pathology in the Alg(+) PAOmucA22 group suggests that alginate production not only impedes pulmonary clearing, but also results in severe lung damage. Positive correlations between IL12 levels and lung macroscopic pathology, and between IL12 and IFN-gamma levels in the Alg(+) PAOmucA22 group, suggested a possible contribution of these pro-inflammatory cytokines to tissue damage. No significant differences were found between the three groups in lung cytokine responses at 24 or 48 h post-infection. However, on comparison within each group at 24 and 48 h post-infection, a significant increase in the pro-inflammatory cytokine IFN-gamma was observed. Higher ratios of IFN-gamma/IL4 and IFN-gamma/IL10, but lower IL10 levels, were also found in all three groups. These results indicate a Th1-predominated immune response in these animals. Such cytokine responses could have aided the clearance of non-mucoid P. aeruginosa, but were not sufficient to alleviate infection by the mucoid variants. Alginate production may promote survival and persistence of this pathogenic micro-organism in the lung.

Acute Disease↗
PubMed1992

Properties determining the potential of naturally occurring and vaccine-induced human antibodies to protect against lethal infection of Pseudomonas aeruginosa.

In order to characterize antibodies responsible for the protection against fatal infection with Pseudomonas aeruginosa we analysed the fine specificity, avidity and protective capacities of naturally occurring anti-lipopolysaccharide (LPS) antibodies in two standard human Ig preparations and of vaccine-induced anti-LPS antibodies in a hyperimmune Ig preparation. Applying competitive binding assays, immunoblotting and an in vivo protection assay, we provide evidence that only preparations from immunized volunteers contain significant amounts of antibodies which confer detectable protection in a murine burn-wound model. Supported by the parallel analysis of monoclonal antibodies, our data suggest that protection by passive immunization with anti-LPS antibodies is mediated by antibodies specific for the LPS O-chain moiety of the corresponding virulent bacterium. Furthermore, our results indicate that protectiveness is restricted to a small population of antibodies with high affinity for particular O-chain epitopes.

Animals↗
PubMed1981

Protection against experimental Pseudomonas aeruginosa infection in mice by active immunization with exotoxin A toxoids.

The immunoprophylactic effect of chemically inactivated Pseudomonas aeruginosa exotoxin A in experimental pseudomonas infections was studied. Exotoxin A toxoids were prepared by Formalin (f-TXD) or glutaraldehyde (g-TXD) treatment. Immunization of mice with three or four doses (10 micrograms each) of f-TXD and the synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (50 micrograms) induced high levels of antiexotoxin A antibodies as measured by passive hemagglutination assay and enzyme-linked immunosorbent assay. Immunization with toxoid alone did not elicit antitoxin. A significant increase in survival time and survival rate (P less than 0.01) was seen in immunized (f-TXD) and in burned and infected mice (50 to 85%) as compared with control mice immunized with formalinized bovine serum albumin (6 to 20%). Virtually 100% survival was obtained when preinfection immunization weas combined with single-dose gentamicin treatment within 24 h of infection. Immunization with g-TXD increased survival time (P less than 0.01) but did not consistently increase survival rate, and the results were not as satisfactory as those with formalinized exotoxin. The data presented indicate that active immunization with formalinized exotoxin A toxoid and adjuvant induced protective immunity to various degrees against infections in mice and could be potentially useful in prophylaxis of P. aeruginosa infections.

ADP Ribose Transferases↗