Pseudomonas Exotoxin Shock

Atik, M

doi:10.1001/jama.1968.03140290026007

Cited by 32 publications

(5 citation statements)

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“…Widely produced by clinical PA strains regardless of immunotype (15,16), it is toxic for tissue cultures (17)(18)(19)(20) and lethal for animals (18,21,22). It has been purified to homogeneity (21,(23)(24)(25)(26), partially characterized (21,23,25), and its mode of action delineated in cell-free systems (27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man.

Pollack¹,

Young²

1979

J. Clin. Invest.

204

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A B S T R A C T Serum antibodies to exotoxin A and type-specific lipopolysaccharide were measured by passive hemagglutination in 52 patients with Pseudomonas aeruginosa septicemia. Their comparative protective activities were evaluated by relating the titers of each at the onset of bacteremia to subsequent outcome. High acute serum antitoxin and antilipopolysaccharide titers (log2 reciprocal mean titers >5) were associated with survival (76% of 17 with high vs. 46% of 24 with low antitoxin titers, P = 0.05; 85% of 13 with high vs. 48% of29 with low antilipopolysaccharide titers, P = 0.03). In contrast, neither antibody titer was significantly associated (P c 0.05) with patients' age or sex, severity ofunderlying disease, presence ofleukopenia, steroid or immunosuppressive therapy. Despite a correlation between acute titers of the two antibodies (r = 0.33, P = 0.06), they appeared to protect independently and additively. Whereas 75% of 8 patients with high antitoxin titers and only 38% of 16 with low titers survived with low antilipopolysaccharide titers (P = 0.10), 100% (6/6), 73% (8/11), and 38% (6/16) survived, respectively, when both, one, or neither antibody was present in high titer (P = 0.01). Furthermore, the association between high acute serum antitoxin titers and survival was more pronounced in patients with rapidly fatal underlying disease (P = 0.06) and leukopenia (P = 0.12) than in more favorable prognostic and immune categories. These data indicate that serum antibodies to exotoxin A and lipopolysaccharide are found in most patients with P. aeruginosa septicemiaThe opinions and assertions contained herein are the private ones of the writers and are not to be construed as official or reflecting the views of the Navy Department or the naval service at large.

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Section: Introductionmentioning

confidence: 99%

Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man.

Pollack¹,

Young²

1979

J. Clin. Invest.

204

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“…P. aeruginosa ETA was first discovered and purified by Liu et al (13). Since then, ETA has proven to be toxic for a wide variety of mammalian cells in vitro (19,21) and lethal for many animal species (2,20). In mice, ETA is approximately 10,000 times more lethal than lipopolysaccharide from P. aeruginosa (22).…”

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confidence: 99%

Protection against Exotoxin A (ETA) and Pseudomonas aeruginosa Infection in Mice with ETA-Specific Antipeptide Antibodies

et al. 1998

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Pseudomonas aeruginosa is an opportunistic pathogen that causes serious and sometimes fatal infections in the compromised host, especially in patients with major trauma or thermal injuries. Exotoxin A (ETA) is the major and most lethal virulence factor produced by this ubiquitous microorganism. In a recent study (H. S. Elzaim, A. K. Chopra, J. W. Peterson, R. Goodheart, and J. P. Heggers, Infect. Immun. 66:2170–2179, 1998), we identified two major epitopes, one within the translocation domain (amino acid [aa] residues 289 to 333) of ETA and another within the enzymatic domain (aa 610 to 638), by using a panel of antipeptide antibodies. Synthetic peptides representing these two epitopes induced ETA-specific antibodies which were able to abrogate the cytotoxic activity of ETA, as measured by incorporation of [3H]leucine into 3T3 fibroblasts. In the present study, these antibodies were tested for the ability to provide protection against ETA and infection with a toxin-producing strain of P. aeruginosa in a mouse model. Antibodies to either of the synthetic peptides conferred protection against ETA. Also, when used for immunization, both peptides induced active immunity to ETA in mice. Antibodies to the peptide representing a region within the enzymatic domain of ETA, in combination with the antibiotic amikacin, enhanced the survival of mice infected with a toxin-producing strain ofP. aeruginosa. Thus, antipeptide antibodies specific for ETA might be paired with antibiotic treatment for passive immunization of patients suffering from P. aeruginosainfection.

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“…The role of extracellular substances of Pseudomonas aeruginosa in the pathogenesis of Pseudomonas infections in humans is not well understood. However, exotoxin A (PA toxin), originally described by Liu et al (12,13), has the potential to be an important virulence factor of P. aeruginosa (4,5,9,18).…”

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confidence: 99%

Temperature-dependent inactivating factor of Pseudomonas aeruginosa exotoxin A

Vasil¹,

Liu²,

Iglewski³

1976

Infect Immun

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The adenosine diphosphate ribosyl transferase activity of Pseudomonas aeruginosa exotoxin A (PA toxin) was found to be rapidly destroyed by heating at 45 to 60 C but not by heating at 70 to 90 C (for at least 30 min). This phenomenon has been previously described for other bacterial toxins (staphylococcal alpha-toxin and Vibrio parahaemolyticus hemolysin) and is termed an Arrhenius effect. In contrast, the Arrhenius effect was not seen when the PA toxin was heat-treated as above and tested for cell toxicity or mouse lethality. Although the PA toxin treated at 70 C for 30 min retained a significant proportion (>70%) of its adenosine diphosphate ribosyl transferase activity, the cell toxicity and mouse lethality of the toxin were virtually abolished. A temperature-dependent inactivating factor that has proteolytic activity and is co-purified with the PA toxin was shown to be responsible for the Arrhenius effect. PA toxin separated from the factor by conventional disc gel electrophoresis or PA toxin preparations lacking the factor did not show the Arrhenius effect.

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Pseudomonas Exotoxin Shock

Cited by 32 publications

References 0 publications

Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man.

Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man.

Protection against Exotoxin A (ETA) and Pseudomonas aeruginosa Infection in Mice with ETA-Specific Antipeptide Antibodies

Temperature-dependent inactivating factor of Pseudomonas aeruginosa exotoxin A

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