Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury

Sawa, Teiji; Yahr, Timothy L.; Ohara, Maria; Kurahashi, Kiyoyasu; Gropper, Michael A.; Wiener-Kronish, Jeanine P.; Frank, Dara W.

doi:10.1038/7391

Cited by 329 publications

(368 citation statements)

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“…4,5 These proteins alter the function of the host cell, assist the microbe to invade, resist phagocytosis, grow in deep tissues and cause disease. [6][7][8][9][10] The T3SS is involved in a range of pathogenic mechanisms and its activity correlates closely with disease progression and outcome. 11 The well-studied plasmid-encoded Ysc of Yersinia is representative of these common virulence systems.…”

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confidence: 99%

Solving the Supply of Resveratrol Tetramers from Papua New Guinean Rainforest Anisoptera Species That Inhibit Bacterial Type III Secretion Systems

Davis

Beattie

et al. 2014

J. Nat. Prod.

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The supply of (−)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screening of a prefractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A. thurifera, and similarly A. polyandra, resulted in three known resveratrol tetramers, (−)-hopeaphenol (1), vatalbinoside A (2), and vaticanol B (3). Compounds 1−3 displayed IC 50 values of 8.8, 12.5, and 9.9 μM in a luminescent reporter-gene assay (YopE) and IC 50 values of 2.9, 4.5, and 3.3 μM in an enzyme-based YopH assay, respectively, which suggested that they could potentially act against the T3SS in Yersinia. The structures of 1−3 were confirmed through a combination of spectrometric, chemical methods, and single-crystal X-ray structure determinations of the natural product 1 and the permethyl ether analogue of 3. The enzymatic hydrolysis of the β-glycoside 2 to the aglycone 1 was achieved through biotransformation using the endogenous leaf enzymes. This significantly enhanced the yield of the target bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (−)-hopeaphenol (1).

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confidence: 99%

Solving the Supply of Resveratrol Tetramers from Papua New Guinean Rainforest Anisoptera Species That Inhibit Bacterial Type III Secretion Systems

Davis

Beattie

et al. 2014

J. Nat. Prod.

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“…In a previous study, it was shown that administration of anti-PcrV antibody (Ab) was able to block the translocation of P. aeruginosa type III-secreted toxins [7]. Anti-PcrV immunoglobulin (Ig)G also exerted therapeutic effects, reducing septic shock and mortality in an animal model of acute P. aeruginosa infection [7,8]. However, the efficacy of anti-PcrV IgG in chronic P. aeruginosa infection has not yet been clarified.…”

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confidence: 99%

“…Expression of these toxins causes epithelial injury and inhibits the host immune response [3,[5][6][7]. PcrV is homologous to the Vantigen (LcrV) found on the surface of Yersinia and appears to be an integral component of the translocation process [7]. In a previous study, it was shown that administration of anti-PcrV antibody (Ab) was able to block the translocation of P. aeruginosa type III-secreted toxins [7].…”

mentioning

confidence: 99%

“…PcrV is homologous to the Vantigen (LcrV) found on the surface of Yersinia and appears to be an integral component of the translocation process [7]. In a previous study, it was shown that administration of anti-PcrV antibody (Ab) was able to block the translocation of P. aeruginosa type III-secreted toxins [7]. Anti-PcrV immunoglobulin (Ig)G also exerted therapeutic effects, reducing septic shock and mortality in an animal model of acute P. aeruginosa infection [7,8].…”

mentioning

confidence: 99%

“…Toxins such as exoenzyme S, T, U and Y are directly transported into eukaryotic cells through the type III secretion system [1][2][3][4]. Expression of these toxins causes epithelial injury and inhibits the host immune response [3,[5][6][7]. PcrV is homologous to the Vantigen (LcrV) found on the surface of Yersinia and appears to be an integral component of the translocation process [7].…”

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confidence: 99%

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Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model

Imamura

Yanagihara²,

Fukuda³

et al. 2007

European Respiratory Journal

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Pseudomonas aeruginosa is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic P. aeruginosa infection.The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic P. aeruginosa infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-a, and interleukin-b concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period.These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic Pseudomonas aeruginosa respiratory infection and may be useful in treating respiratory diseases.

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Longitudinal Development of Mucoid <EMPH>Pseudomonas aeruginosa</EMPH> Infection and Lung Disease Progression in Children With Cystic Fibrosis

Li¹

2005

JAMA

479

419

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Context Although Pseudomonas aeruginosa is the most common virulent respiratory pathogen in cystic fibrosis (CF), the longitudinal development of P aeruginosa infection and its effect on antibody responses and lung disease progression in children with CF remain unclear.Objective To prospectively examine the epidemiology of P aeruginosa infection and its impact on CF pulmonary morbidity. Design, Setting, and PatientsWe prospectively evaluated 56 CF patients at 2 CF centers in Madison and Milwaukee, Wis, from birth up to age 16 years between April 15, 1985, and April 15, 2004, with diagnoses made through the Wisconsin CF Neonatal Screening Project.Main Outcome Measures Timing of nonmucoid P aeruginosa and mucoid P aeruginosa acquisition was assessed by first positive result. Longitudinal development from no P aeruginosa to nonmucoid P aeruginosa and from nonmucoid P aeruginosa to mucoid P aeruginosa was examined. Outcome measurements included antibody titers, respiratory symptoms, quantitative chest radiography, and pulmonary function tests. ResultsSixteen patients (29%) acquired nonmucoid P aeruginosa in the first 6 months of life. The age-specific prevalence of mucoid P aeruginosa increased markedly from age 4 to 16 years. Nonmucoid and mucoid P aeruginosa were acquired at median ages of 1.0 and 13.0 years, respectively. In contrast with the short transition time from no P aeruginosa to nonmucoid P aeruginosa, the transition time from nonmucoid to mucoid P aeruginosa was relatively long (median, 10.9 years) and could be slightly extended by brief/low anti-P aeruginosa antibiotic treatment. Antibody titers increased with both transitions, but the deterioration in cough scores, chest radiograph scores, and pulmonary function correlated best with transition from nonmucoid to mucoid P aeruginosa.Conclusions Early prevention and detection of nonmucoid and mucoid P aeruginosa are critical because of early acquisition and prevalence. There is a window of opportunity for suppression and possible eradication (by aggressive anti-P aeruginosa treatment) of initial nonmucoid P aeruginosa. Mucoid P aeruginosa plays a much greater role in CF lung disease progression than nonmucoid P aeruginosa. Antibody titers, cough scores, and chest radiographs are early signs of nonmucoid P aeruginosa and especially mucoid P aeruginosa stages.

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Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury

Cited by 329 publications

References 38 publications

Solving the Supply of Resveratrol Tetramers from Papua New Guinean Rainforest Anisoptera Species That Inhibit Bacterial Type III Secretion Systems

Solving the Supply of Resveratrol Tetramers from Papua New Guinean Rainforest Anisoptera Species That Inhibit Bacterial Type III Secretion Systems

Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model

Longitudinal Development of Mucoid <EMPH>Pseudomonas aeruginosa</EMPH> Infection and Lung Disease Progression in Children With Cystic Fibrosis

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