Prospective study of serum antibodies to Pseudomonas aeruginosa exoproteins in cystic fibrosis

Hollsing, Annika; Granström, Marta; Vasil, M. L.; Wretlind, Bengt; Strandvik, Birgitta

doi:10.1128/jcm.25.10.1868-1874.1987

Cited by 92 publications

(30 citation statements)

References 31 publications

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“…The immune response to P. aeruginosa has been used as a tool to identify chronic infections in CF since the early 1970s. [30][31][32] Mucoid P. aeruginosa strains induce a more pronounced antibody response than non-mucoid strains, 33 but it is also clear that antibody titres may vary during periods of active infection, 34 and therefore, result interpretation is difficult in the different contexts of infection in CF (early, intermittent and chronic). Some recent data from longitudinal studies indicated that antibody titers may rise significantly earlier than isolation of P. aeruginosa in oropharyngeal cultures.…”

Section: Discussionmentioning

confidence: 99%

The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/infection in cystic fibrosis

Filho

Tateno

Martins

et al. 2007

Pediatric Pulmonology

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PCR identified a higher number of patients with P. aeruginosa than serology and conventional culture, but the difference did not reach statistical significance. Any of the combination methods that included PCR resulted in significantly statistical differences in relation to isolated microbiological or serology methods, but not to the PCR method alone, suggesting that PCR may be the main additive method for P. aeruginosa identification.

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Section: Discussionmentioning

confidence: 99%

The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/infection in cystic fibrosis

Filho

Tateno

Martins

et al. 2007

Pediatric Pulmonology

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“…1). Demonstration that the levels of anti-ETA antibodies in the blood of chronically infected CF patients fluctuate (22) might lead one to expect this result. However, other studies suggest that the detection of these gene products is somewhat surprising.…”

Section: Discussionmentioning

confidence: 99%

“…This bacterium plays a key role in the destruction of the lungs of CF patients through its ability to persist after initial colonization (6,37,55,56). P. aeruginosa produces a number of virulence factors, both cell associated and secreted, which have been linked to initial colonization of and persistence in the CF lung (7,8,16,22,24,26,35,39,57). Among these are exotoxin A (ETA), elastase, exoenzyme S, alkaline proteinase, phospholipase C, and alginate (7,8,16,22,24,26,33,35,39,57).…”

mentioning

confidence: 99%

“…Further, high levels of antibody to ETA in serum correlate with exacerbations of lung infection (35). Fluctuating levels of anti-ETA antibody in the sera of CF patients chronically infected with P. aeruginosa suggest that ETA production may be regulated in this environment (22). To date, several genes which are involved in regulating the production of ETA have been identified.…”

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Association between transcript levels of the Pseudomonas aeruginosa regA, regB, and toxA genes in sputa of cystic fibrosis patients

et al. 1994

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In this study, we examined the regulation of exotoxin A (ETA) production by Pseudomonas aeruginosa during chronic lung infections of cystic fibrosis (CF) patients. We used a recently developed technique termed population transcript accumulation in hybridization studies with RNA extracted from sputa. With this technique, we demonstrated that the structural gene for ETA, toxA, as well as two genes encoding positive regulators of ETA synthesis, regA and regB, were expressed in the lungs of CF patients infected with P. aeruginosa. These genes were always expressed together, never alone or in pairs, suggesting coincident expression and a possible regulatory role for regA and regB in this environment. Fluctuations in the levels of the three gene products were observed among samples, consistent with a regulatory phenomenon. The level of regB RNA detected never exceeded that ofregA, although the ratio of regA RNA to regB RNA detected did change between samples. These observations are in agreement with in vitro observations which have shown that regB is located 3' to regA in an operon which is expressed from two independently regulated promoters located upstream of regA. The presence of high levels of toxA, regA, and regB RNAs in some sputum samples prompted us to look for hyperproducing-toxin strains in the sputa of CF patients. In vitro, one such strain, 4384, had a transcript accumulation pattern for toxA, regA, and regB similar to that of a laboratory hyperproducer of ETA, strain PA103. These observations suggest that regA and regB are involved in the regulation of ETA production in strains of P. aeruginosa infecting the lungs of CF patients and that some of these strains may regulate ETA production in a manner similar to that of the hyperproducing-ETA strain PA103.

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“…Antigenic properties of exoproducts P. aeruginosa produces a number of secreted virulence factors including exotoxin A, exoenzyme S, proteases I (neutral protease) and III (alkaline phosphatase), elastase, hemolysins (thermolabile phosphatase C and thermostable acid glycolipid), enter- Table 1 Probable role of extracellular products of P. aeruginosa in virulence and immunogenicity Extracellular antigen Role in virulence Antibody or protective response Reference Proteases : (i) Elastase Induces hemorrhagic lesions and necrosis, Abs in patients with chronic and/or active [18^20] tissue invasion, destruction of host defenses, P. aeruginosa infections; provide protections against e.g. complements and opsonins severe lung lesions in animal models (ii) Alkaline protease Destruction of non-speci¢c host defenses, Abs detected in burn wound patients [21] tissue invasion Phospholipase C Destruction of pulmonary surfactant Rise in Ab titer in CF patients colonized with [22,23] Generation of in£ammatory mediators P. aeruginosa, and in animal model infections Rhamnolipids…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosa antigens as potential vaccines

Stanislavsky

1997

FEMS Microbiology Reviews

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Pseudomonas aeruginosa is one of the most important opportunistic bacterial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeability of the outer membrane and the presence of numerous multiple drug efflux pumps. Various cell-associated and secreted antigens of P. aeruginosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consisting predominantly of alginate, was found to be heterogeneous in terms of size and immunogenicity. High molecular mass alginate components (30^300 kDa) appear to contain conserved epitopes while lower molecular mass alginate components (10^30 kDa) possess conserved epitopes in addition to unique epitopes. Surface-exposed antigens including Oantigens (O-specific polysaccharide of LPS) or H-antigens (flagellar antigens) have been used for serotyping due to their highly immunogenic nature. Chemical structures of repeating units of O-specific polysaccharides have been elucidated and these data allowed the identification of 31 chemotypes of P. aeruginosa. Conserved epitopes among all serotypes of P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce crossprotective immunity in mice against different P. aeruginosa immunotypes. To examine the protective properties of OM proteins, a vaccine containing P. aeruginosa OM proteins of molecular masses ranging from 20 to 100 kDa has been used in pre-clinical and clinical trials. This vaccine was efficacious in animal models against P. aeruginosa challenge and induced high levels of specific antibodies in human volunteers. Plasma from human volunteers containing anti-P. aeruginosa antibodies provided passive protection and helped the recovery of 87% of patients with severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the efficacy of ribosomal vaccines in humans is not yet known. A number of recent studies indicated the potential of some P. aeruginosa antigens that deserve attention as new vaccine candidates. The outer core of LPS was implicated to be a ligand for binding of P. aeruginosa to airway and ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inner core are highly conserved and it has been demonstrated to be surface-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of researchers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed proteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly conserved protein, WbpM, and P. aeruginosa with a deficiency in this protein produces only rough LPS and became serum sensit...

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Prospective study of serum antibodies to Pseudomonas aeruginosa exoproteins in cystic fibrosis

Cited by 92 publications

References 31 publications

The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/infection in cystic fibrosis

The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/infection in cystic fibrosis

Association between transcript levels of the Pseudomonas aeruginosa regA, regB, and toxA genes in sputa of cystic fibrosis patients

Pseudomonas aeruginosa antigens as potential vaccines

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