Chronic Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis Patients

Döring, Gerd

doi:10.1007/978-1-4615-3036-7_13

Cited by 36 publications

(28 citation statements)

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“…Nevertheless, we cannot rule out the possibility that ChxA could mediate enterotoxicity in humans, as some of the chxA-positive strains used in this study are of clinical origin. ExoA is reported as an important virulence factor in P. aeruginosa infections like septicemia, lung, renal, and liver infections (35)(36)(37)(38). The contribution of ChxA as a virulence factor to organ dysfunction has not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

et al. 2013

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e Cholix toxin (ChxA) is a recently discovered exotoxin in Vibrio cholerae which has been characterized as a third member of the eukaryotic elongation factor 2-specific ADP-ribosyltransferase toxins, in addition to exotoxin A of Pseudomonas aeruginosa and diphtheria toxin of Corynebacterium diphtheriae. These toxins consist of three characteristic domains for receptor binding, translocation, and catalysis. However, there is little information about the prevalence of chxA and its genetic variations and pathogenic mechanisms. In this study, we screened the chxA gene in a large number (n ‫؍‬ 765) of V. cholerae strains and observed its presence exclusively in non-O1/non-O139 strains (27.0%; 53 of 196) and not in O1 (n ‫؍‬ 485) or O139 (n ‫؍‬ 84). Sequencing of these 53 chxA genes generated 29 subtypes which were grouped into three clusters designated chxA I, chxA II, and chxA III. chxA I belongs to the prototype, while chxA II and chxA III are newly discovered variants. ChxA II and ChxA III had unique receptor binding and catalytic domains, respectively, in comparison to ChxA I. Recombinant ChxA I (rChxA I) and rChxA II but not rChxA III showed variable cytotoxic effects on different eukaryotic cells. Although rChxA II was more lethal to mice than rChxA I when injected intravenously, no enterotoxicity of any rChxA was observed in a rabbit ileal loop test. Hepatocytes showed coagulation necrosis in rChxA I-or rChxA II-treated mice, seemingly the major target for ChxA. The present study illustrates the potential of ChxA as an important virulence factor in non-O1/non-O139 V. cholerae, which may be associated with extraintestinal infections rather than enterotoxicity.

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Section: Discussionmentioning

confidence: 99%

Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

et al. 2013

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“…The detection limits were 0.3 £/1 for alkaline protease and 0.26 g/l for exotoxin A, i. e. in the same ränge äs those of the elastase assay. Radioimmunoassays of alkaline protease (17) and exotoxin A (18) showed good lower detection limits of around one /l, but had the disadvantage of using radiolabelled products. The enzyme immunoassay for exotoxin A developed by Schultz (15) also had good The precision of the assay was comparable with that of elastase (tab.…”

Section: Discussionmentioning

confidence: 99%

Immunoenzymometric Assays for Alkaline Protease and Exotoxin A from Pseudomonas aeruginosa: Development and Use in Detecting Exoproteins in Clinical Isolates from Patients with Cystic Fibrosis

Jaffar‐Bandjee

Carrère²,

Bally³

et al. 1994

CCLM

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JafFar-Bandjee et al.: Exoproteins of Pseudomonas aeruginosa: Immunoassays in cultures from cystic fibrosis sputa 893Eur. J. Clin. Chem. Clin. Biochcm. Vol. 32, 1994, pp. 893-899 © 1994 Summary: Using immunoenzymometric assays, the production of elastase, alkaline protease and exotoxin A was determined in culture supernatants of 35 strains of Pseudomonas aeruginosa isolated frorn patients suffering from cystic fibrosis. The assays were simple, specific, sensitive and reproducible, and permitted the determination of low levels of exoproteins. A large strain variability of exoprotein production was found. Most of the strains secreted all three exoproteins, but six out of the 35 strains (17%) did not secrete at least one of the three (< 0.3 §/1). A significant correlation was observed between elastase and exotoxin A productions (r = 0.697, p < 0.001). Introductioii

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“…The loss of the O side chain is thought to allow the organism to avoid host adaptive immune responses. One factor often overlooked in the analysis of P. aeruginosa virulence in the CF lung is that these patients are quite immunocompetent and make potent immune responses to many cell surface and secreted virulence factors [56,57], usually leading to inactivation of their toxicity or virulence-promoting activity. Of note, increased antibody responses to P. aeruginosa in CF patients are associated with a worse clinical status, probably resulting from the inflammatory damage ensuing from the binding of antibodies and/or complement to the bacterial antigens.…”

Section: Establishment Of Chronic Infectionmentioning

confidence: 99%

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Campodónico

Gadjeva

Paradis-Bleau

et al. 2008

Trends in Molecular Medicine

100

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Defective expression or function of the cystic fibrosis transmembrane conductance regulator (CFTR) underlies the hypersusceptibility of cystic fibrosis (CF) patients to chronic airway infections, particularly with Pseudomonas aeruginosa. CFTR is involved in the specific recognition of P. aeruginosa, thereby contributing to effective innate immunity and proper hydration of the airway surface layer (ASL). In CF, the airway epithelium fails to initiate an appropriate innate immune response, allowing the microbe to bind to mucus plugs that are then not properly cleared because of the dehydrated ASL. Recent studies have identified numerous CFTR-dependent factors that are recruited to the epithelial plasma membrane in response to infection and that are needed for bacterial clearance, a process that is defective in CF patients hypersusceptible to infection with this organism. Pseudomonas aeruginosa in cystic fibrosisCystic fibrosis (CF) is unique among human genetic disorders in that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a protein whose primary function described to date has been to regulate conductance of ions in and out of cells and intracellular vacuoles, lead to hypersusceptibility to chronic lung infection. Human diseases wherein individuals homozygous for mutant genes are predisposed to infections serve as a firm foundation for understanding the molecular, cellular, physiologic and immunologic aspects of normal and compromised resistance to infection. CF is not just a prime example of how we can learn about normal and pathologic states; it could, in fact, be the only known human genetically determined disease wherein infection with a single pathogen -Pseudomonas aeruginosa -drives the vast majority of morbidity, clinical deterioration and ultimately life-shortening mortality encountered in this disease. In humans with significant compromises to their immune system, such as advanced AIDS, we would normally expect to see a plethora of pathogens take advantage of this debilitated state, but this is not the case in CF.CF is characterized by the emergence and persistence of (and, ultimately, the inability to clear) chronic infection with a variant of P. aeruginosa (mucoid P. aeruginosa) that overproduces a surface polysaccharide known as alginate. The organism undergoes other significant genetic adaptations and selections within the CF lung, and it is the emergence of mucoid P. aeruginosa that is the primary determinant of the clinical course of this disease [1,2]. In those individuals with either an uncommon but fortuitous protective immune response to specific P. aeruginosa antigens [3,4] Histopathologic basis for defining relevant interactions between P.aeruginosa and the CF airway epitheliumAlthough CF is a multisystem disease characterized by GI and nutritional abnormalities, salt loss syndromes and male urogenital abnormalities, the major clinical problem for CF patients is chronic sinopulmonary disease. Therefore, relying on observations made fr...

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Chronic Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis Patients

Cited by 36 publications

References 193 publications

Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

Immunoenzymometric Assays for Alkaline Protease and Exotoxin A from Pseudomonas aeruginosa: Development and Use in Detecting Exoproteins in Clinical Isolates from Patients with Cystic Fibrosis

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

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