The effect of Pseudomonas aeruginosa cytotoxin and toxin A on human polymorphonuclear leukocytes

Bishop, Monica; Baltch, Aldona L.; Hill, L. A.; Smith, Raymond P.; Lutz, F.; Pollack, Matthew

doi:10.1099/00222615-24-4-315

Cited by 18 publications

(9 citation statements)

References 21 publications

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“…Recent morphological evidence shows that the plant toxins ricin and abrin inflict typical apoptotic changes in lymphoid and intestinal tissue (19). Pseudomonas cytotoxin and exotoxin A also cause morphological changes that resemble programmed cell death (7). In parallel studies with U937 cells, we found that TNF, DTx, ricin, and Pseudomonas exotoxin A all induce DNA fragmentation, widespread membrane blebbing, and eventual cell lysis (M. P. Chang and B. J. Wisnieski, unpublished data).…”

Section: Discussionmentioning

confidence: 53%

Comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

Chang

Wisnieski

1990

Infect Immun

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The mechanism by which tumor necrosis factor alpha (TNF) initiates tumor cell destruction is unknown.Having established that a brief drop in extracellular pH enhances the killing activity of TNF, our next objective was to explore whether TNF-induced cell death is dependent on endosomal acidification. Diphtheria toxin (DTx), a well-characterized acid-dependent cytotoxin, served as an indicator of the effectiveness of each treatment condition. Studies with lysosomotropic agents demonstrated that the cytotoxic pathway of TNF can operate independently of low pH exposure in contrast to the lethal pathway of DTx. When NH4CI-treated cells were exposed to TNF at low pH, the level of killing increased twoto threefold over that attained with cells maintained at neutral pH (either with or without NH4Cl). Furthermore, inhibition of metabolic processes by sodium azide in combination with 2-deoxyglucose severely reduced DTx killing but stimulated TNF killing. Despite these differences, TNF and DTx provoked extensive internucleosomal DNA cleavage in prelytic target cells. Inhibitors of nuclear poly(ADP-ribose) transferase also evoked similar levels of cellular resistance to both cytotoxins. Models for DTx-and TNF-induced cytolysis are discussed in view of these new discoveries.

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Section: Discussionmentioning

confidence: 53%

Comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

Chang

Wisnieski

1990

Infect Immun

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“…Among enterics and pseudomonads, some species (especially P. aeruginosa) have been shown to be tissue invasive (9), elaborate extracellular leukotoxins (5,7,52) and hemolysins (10,50), suppress lymphocyte proliferation (32), inactivate complement components (62), inactivate plasma alpha-1 -proteinase inhibitor (43,47), degrade immunoglobulins TgG and TgA (17,43), kill fibroblasts (43), inhibit mammalian cell protein synthesis (31), degrade basement membrane laminin (25), release potent enterotoxins and endotoxins (9), and elaborate coUagenolytic (26,43) and other proteolytic enzymes (10,43,44).…”

Section: Discussionmentioning

confidence: 99%

Yeasts, enteric rods and pseudomonads in the subgingival flora of severe adult periodontitis

Slots

Rams

Listgarten

1988

Oral Microbiology and Immunology

269

199

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The subgingival occurrence of yeasts and species of Enterobacteriacae and Pseudomonas was studied in 500 adults with severe periodontitis. All subjects had sites non‐responding or “refractory” to conventional periodontal therapy. Most subjects had received one or more courses of broad‐spectrum systemic antibiotics. Subgingival microbial samples were collected with paper points and transported in VMGA III. The bacterial samples were plated on enriched brucella blood agar and incubated anaerobically, and on TSBV, TBC, and Sabouraud agar, which were incubated in 10% CO2. Yeasts were speciated using the API 20C micro‐method system and the germ tube test (for Candida albicans). Enteric organism's and pseudomonads were speciated with the API 20E kit system. Yeasts, enteric rods and pseudomonads were subjected to antibiotic susceptibility testing. The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, and Bacteroides intermedium was also determined in the patients studied. In the 500 periodontitis patients, yeasts were detected in 84 (16.8%), enteric rods or pseudo‐monads in 51 (10.2%), and both yeasts and enterics or pseudomonads in 6 (1.2%). Candida albicans comprised 83.3% of the isolated yeasts. Enterobacteriaceae averaged 21–39% of the cultivable flora in culture‐positive cases, with Enterobacter cloacae, Enterobacter agglomerans, Proteus mirabilis, Klebsietta pneumonias, and Klebsiella oxytoca being the most frequent species. Pseudomonas aeruginosa was isolated from 10 patients, averaging 23.4% of the cultivable subgingival flora. All Candida isolates, and 86–95% of the enteric rods and pseudomonads, were resistant to 1 μg/ml of tetracycline, penicillin G, and erythromycin. In patients positive for yeasts, enteric rods or pseudomonads, A. actinomycetemcomitans was isolated from about one‐fifth, B. intermedius from about one‐third, and B. gingivalis from 5% of the individuals. The present findings suggest that yeasts or enteric rods or pseudomonads occur in the subgingival flora of about one‐third of “refractory” adult periodontitis patients. We caution against using antibiotics without prior microbiological screening in treating this patient group.

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“…Loss of cell volume coincided with nuclear accumulation of ethidium homodimer-1 (see the video in the supplemental material). Lysis of neutrophils by PA99null at later times was likely due to other factors produced by P. aeruginosa that have been shown to kill neutrophils or have been hypothesized to have such activity (5,37). Ethidium homodimer-1 staining was not observed in uninfected cells (data not shown).…”

Section: Vol 76 2008 P Aeruginosa Induces Localized Immunosuppressmentioning

confidence: 91%

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia

et al. 2008

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Hospital-acquired bacterial pneumonia is a common and serious complication of modern medical care. Many aspects of such infections remain unclear, including the mechanisms by which invading pathogens resist clearance by the innate immune response and the tendency of the infections to be polymicrobial. Here, we used a mouse model of infection to show that Pseudomonas aeruginosa, a leading cause of hospital-acquired pneumonia, interferes with the ability of recruited phagocytic cells to eradicate bacteria from the lung. Early in infection, phagocytic cells, predominantly neutrophils, are recruited to the lungs but are incapacitated when they enter the airways by the P. aeruginosa toxin ExoU. The resulting paucity of functioning phagocytes allows P. aeruginosa to persist within the lungs and results in local immunosuppression that facilitates superinfection with less-pathogenic bacteria. Together, our results provide explanations for previous reports linking ExoU-secreting P. aeruginosa with more severe pulmonary infections and for the tendency of hospital-acquired pneumonia to be polymicrobial.Hospital-acquired pneumonia (HAP) is a common and frequently lethal complication of admission to an acute medical care facility. HAP infections occur in 0.5 to 2% of hospitalized patients (30,33) and are associated with mortality rates of approximately 30% (6,13,41,54). HAP is usually caused by bacterial pathogens, and in 26 to 67% of cases the etiology is polymicrobial (3,8,39). While the reasons for this are unclear, the coexistence of multiple species of bacteria within the lungs of patients may contribute to the high mortality associated with this disease.The gram-negative bacterium Pseudomonas aeruginosa is the leading cause of HAP in patients undergoing mechanical ventilation (referred to as ventilator-associated pneumonia [VAP]) (40). Interestingly, infection with P. aeruginosa, as opposed to infection with most other bacterial species, is an independent risk factor for death in patients with VAP (23). Although a high incidence of antibiotic resistance among P. aeruginosa strains contributes to the excess mortality associated with this bacterium, its intrinsic virulence also likely plays a role. Even VAP patients treated with antimicrobial agents to which their P. aeruginosa isolates were susceptible had a relapse rate of 18% (42). This suggests that P. aeruginosa elaborates potent virulence determinants that are adept at neutralizing the host immune response, resulting in persistent bacterial infections with poor outcomes.Despite the severity of HAP caused by P. aeruginosa, much remains unknown about the mechanisms by which this bacterium persists in the lungs and causes the tissue damage and inflammation associated with pneumonia. P. aeruginosa elaborates a number of virulence factors that may augment the disease process (12, 45), including a type III secretion system, which has been associated with more-severe disease in patients with HAP (18,44). Via a type III secretion system, some strains of P. aeruginosa injec...

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The effect of Pseudomonas aeruginosa cytotoxin and toxin A on human polymorphonuclear leukocytes

Cited by 18 publications

References 21 publications

Comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

Comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

Yeasts, enteric rods and pseudomonads in the subgingival flora of severe adult periodontitis

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia

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