Production of the Pseudomonas aeruginosa neuraminidase is increased under hyperosmolar conditions and is regulated by genes involved in alginate expression.

Cacalano, Grace; Kays, Michael B.; Saiman, Lisa; Prince, Alice

doi:10.1172/jci115791

Cited by 81 publications

(67 citation statements)

References 51 publications

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“…The number of airway epithelial cells with accessible asialoGM1 residues is significantly greater in the cells obtained from CF patients, than in the respiratory epithelial cells from normal subjects. P. aeruginosa produce a number of extracellular products including a neuraminidase which can modify epithelial surfaces (3,21 ). The number of asialoGM and GM1 residues were quantified after the epithelial cells were exposed to P. aeruginosa stationary phase culture supernatants.…”

Section: Resultsmentioning

confidence: 99%

“…The availability of asialoGM receptors on 17% of CF cells but only 3% of normal cells after exposure to accumulated Pseudomonas exoproducts suggests that the ability of the organism to modify the epithelium may be important in establishing infection. The activity of P. aeruginosa exoproducts, which are specifically expressed in the hyperosmolar milieu ofthe CF lung may further expose receptors on other gangliosides (21 ). The effects of the bacterial neuraminidase in vivo may be significantly enhanced in the presence of surfactant within the lung (A.…”

Section: Discussionmentioning

confidence: 99%

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Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.

Saiman¹,

Prince²

1993

J. Clin. Invest.

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326

228

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The basis for the unique association of Pseudomonas aeruginosa and the cystic fibrosis (CF) lung has remained obscure despite major advances in the understanding of the molecular genetic cause of this disease. There is evidence to suggest that abnormalities in CF transmembrane conductance regulator function result in alterations in the glycosylation of epithelial components. The number ofasialoGMl residues, as representative of a class of glycolipids which contain a GalNAcB14Gal sequence for P. aeruginosa attachment, was quantified by flow cytometric studies of respiratory epithelial cells in primary culture from both CF patients and normal subjects. Superficial asialoGMl was detected on 12% of the CF cells as compared with 2.9% of the cells from normal control subjects (P = 0.03, x' = 4.73), and more asialoGMl residues were exposed on CF cells after modification by P. aeruginosa exoproducts. AsialoGMl, but not the sialylated glycolipid GM1, was demonstrated to be a receptor for I2I-labeled P. aeruginosa pilin, a major adhesin for this organism, and exogenous asialoGMl was found to competitively inhibit P. aeruginosa adherence to epithelial cells, thus, confirming the biological role of the asialoGMl receptor. Quantitative and qualitative differences in the sialylation of superficial glycolipids in CF epithelial cells may directly contribute to the colonization of the CF lung by P. aeruginosa. (J. Clin. Invest. 1993. 92:1875-1880

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.

Saiman¹,

Prince²

1993

J. Clin. Invest.

Self Cite

326

228

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“…Bacterial sialidases cleave terminal, non-reducing sialic acid residues from sialoglycoconjugates. The precise role of these enzymes is unknown, but it has been suggested that they act as generalised virulence determinants [18] in that the release of sialic acid may expose cryptic carbohydrate binding sites for the invading organism [19,20] and break down mucosal defence barriers of the host [21]. Furthermore, production of sialidase may be a critical factor in the provision of free sialic acid, a fermentable carbohydrate source for bacterial proliferation [18,22,23].…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterisation of sialidase from a strain of Streptococcus oralis

Byers¹,

Tarelli²,

Homer³

et al. 2000

Journal of Medical Microbiology

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Streptococcus oralis, the most virulent of the viridans streptococci, produces a sialidase and this exo-glycosidase has been implicated in the disease process of a number of pathogens. The sialidase of S. oralis strain AR3 was purified in order to understand the characteristics of this putative virulence determinant. The enzyme isolated as a high mol. wt aggregate (c. 325 kDa) was purified 4520-fold from late exponential phase cultures by a combination of ultrafiltration, ammonium sulphate precipitation, ionexchange and gel filtration chromatography. The sialidase component had a mol. wt of 144 kDa as determined by SDS-PAGE analysis. The purified sialidase released Nacetylneuraminic acid from a range of sialoglycoconjugates including human AE 1 -acid glycoprotein, bovine submaxillary mucin, colominic acid and sialyl-AE2,3-and sialyl-AE2,6-lactose. Also, N-glycolylneuraminic acid was cleaved from bovine submaxillary mucin. The sialidase had a K m of 11.8 ìM for AE 1 -acid glycoprotein, was active over a broad pH range with a pH optimum of 6.0 and cleaved AE2,3-, AE2,6-and AE2-8-sialyl glycosidic linkages with a marked preference for AE2,3-linkages. The enzyme was competitively inhibited by the sialic acid derivative, 2,3-dehydro-N-acetylneuraminic acid, with a K IC of 1.2 ìM. The characteristics of the purified sialidase would support a nutritional role for this enzyme that may be significant in the proliferation of this organism in the oral cavity and at extra-oral sites in association with life-threatening infections.

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“…Neuraminidase, which cleaves terminally-positioned sialic acid residues, is produced by many bacteria and viruses, and is recognized as pathogenic in certain of these [27]. It may be relevant that the gene encoding neuraminidase expression, nanA, is upregulated under conditions of hyperosmolarity [10]. Although data confirming the role of the enzyme in vivo are lacking, CF airway fluid [28,29] may encourage nanA expression.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the baseline increase in aGM1 levels on CF cells, the P. aeruginosa exoproduct, neuraminidase, may further increase the availability of such receptors by cleaving terminal sialic acid residues from cell surface gangliosides. Increased P. aeruginosa adherence has been reported after exposure of cultured epithelial cells to bacterial exoproducts or purified neuraminidase [5,10].…”

mentioning

confidence: 99%

Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition

Davies

Dewar²,

Bush³

et al. 1999

Eur Respir J

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Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition. J. Davies, A. Dewar, A. Bush, T. Pitt, D. Gruenert, D.M. Geddes, E.W.F.W. Alton. #ERS Journals Ltd 1999. ABSTRACT: The high incidence of colonization of the cystic fibrosis (CF) airway with Pseudomonas aeruginosa has been attributed to several mechanisms including increased numbers of asialoglycolipid receptors, which may be further increased by exposure to the bacterial exoproduct, neuraminidase. This study examined whether the adherence of P. aeruginosa to fresh CF respiratory epithelial cells can be reduced in vitro by anti-asialoGM1 (anti-aGM1) antibody, neuraminidase inhibition, or the use of asialoGM1 tetrasaccharide as a competitive inhibitor.CF nasal epithelial cells were incubated with a nonmucoid strain of P. aeruginosa, in the presence or absence of a polyclonal anti-aGM1 antibody, the neuraminidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid (DANA), or the tetrasaccharide moiety of aGM1. Adherence of bacteria to the apical surface of ciliated epithelial cells was quantified using scanning electron microscopy. Incubation of the cells with bacteria in the presence of either anti-aGM1 antibody or DANA significantly reduced bacterial adherence by 51(7)%, (p<0.01), and 34(9)%, (p<0.01), respectively. In contrast, no significant effect on P. aeruginosa binding was seen in the presence of aGM1 tetrasaccharide.The data are consistent with previous studies on cultured cells, and suggest that the in vivo effects of such interventions should be explored as potential mechanisms to reduce Pseudomonas aeruginosa colonization in cystic fibrosis. Eur Respir J 1999; 13: 565±570.

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Production of the Pseudomonas aeruginosa neuraminidase is increased under hyperosmolar conditions and is regulated by genes involved in alginate expression.

Cited by 81 publications

References 51 publications

Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.

Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.

Isolation and characterisation of sialidase from a strain of Streptococcus oralis

Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition

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