Structural basis for oligosaccharide-mediated adhesion of P.
aeruginosa in the lungs of cystic fibrosis patients

D 2003

Structural basis for oligosaccharide-mediated adhesion of P. aeruginosa in the lungs of cystic fibrosis patients

MITCHELL, Edward; Corrine HOULES; Charles SABIN; Michaela WIMMEROVÁ; Catherine GAUTIER et. al.

Basic information

Original name

Structural basis for oligosaccharide-mediated adhesion of P. aeruginosa in the lungs of cystic fibrosis patients

Authors

MITCHELL, Edward; Corrine HOULES; Charles SABIN; Michaela WIMMEROVÁ; Catherine GAUTIER; Serge PEREZ; Albert M. WU; Nechama GILBOA-GARBER and Anne IMBERTY

Edition

Grenoble, France, 12th European Carbohydrate Symposium, p. 61-61, 2003

Publisher

CERMAV-CNRS

Other information

Language

English

Type of outcome

Proceedings paper

Field of Study

10600 1.6 Biological sciences

Country of publisher

France

Confidentiality degree

is not subject to a state or trade secret

RIV identification code

RIV/00216224:14310/03:00008868

Organization unit

Faculty of Science

Keywords in English

Pseudomonas aeruginosa; lectin; microcalorimetry; crystal structure; cystic fibrosis

Abstract

In the original language

The galactose- and fucose-binding (PA-IL and PA-IIL) lectins of Pseudomonas aeruginosa contribute to the virulence of this pathogenic bacterium, which is a major cause of morbidity and mortality in cystic fibrosis (CF) patients via chronic lung colonisation. CF gene mutations increase cell surface fucosylation and CF patients also display modifications in their respiratory and salivary mucins with a higher percentage of sialylated and sulphated oligosaccharides. These cystic fibrosis mucins and cell surface glycoconjugates carry fucose as the terminal sugar residue. Since the P. aeruginosa lectins have been characterised to reveal an outstandingly high affinity of PA-IIL for fucose, they can serve as binding targets for binding by PA-IIL [1]. Precise three-dimensional knowledge of the lectin sugar binding site, through protein crystallography at high resolution, has allowed the unusually high affinity to be understood and shown a novel sugar binding mode. Subsequent modelling studies, based on the fucose complex structure, and binding studies have demonstrated that the preferred ligands of this bacterial lectin belong to the Lea series. Such structure-based knowledge could be used for the design of efficient anti-bacterial compounds and, furthermore, the unusually high affinity interaction of this novel binding mode suggests that PA-IIL may be a useful target for oligosaccharide-based therapeutics.

Links

LN00A016, research and development project

Name: BIOMOLEKULÁRNÍ CENTRUM

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular Center

Cite

MITCHELL, Edward; Corrine HOULES; Charles SABIN; Michaela WIMMEROVÁ; Catherine GAUTIER; Serge PEREZ; Albert M. WU; Nechama GILBOA-GARBER and Anne IMBERTY. Structural basis for oligosaccharide-mediated adhesion of P. aeruginosa in the lungs of cystic fibrosis patients. In 12th European Carbohydrate Symposium. Grenoble, France: CERMAV-CNRS, 2003, p. 61.

@inproceedings{488307,
   author = {Mitchell, Edward and Houles, Corrine and Sabin, Charles and Wimmerová, Michaela and Gautier, Catherine and Perez, Serge and Wu, Albert M. and GilboaandGarber, Nechama and Imberty, Anne},
   address = {Grenoble, France},
   booktitle = {12th European Carbohydrate Symposium},
   keywords = {Pseudomonas aeruginosa; lectin; microcalorimetry; crystal structure; cystic fibrosis},
   language = {eng},
   location = {Grenoble, France},
   pages = {61-61},
   publisher = {CERMAV-CNRS},
   title = {Structural basis for oligosaccharide-mediated adhesion of P. aeruginosa in the lungs of cystic fibrosis patients},
   year = {2003}
}

TY  - CONF
ID  - 488307
AU  - Mitchell, Edward - Houles, Corrine - Sabin, Charles - Wimmerová, Michaela - Gautier, Catherine - Perez, Serge - Wu, Albert M. - Gilboa-Garber, Nechama - Imberty, Anne
PY  - 2003
TI  - Structural basis for oligosaccharide-mediated adhesion of P. aeruginosa in the lungs of cystic fibrosis patients
PB  - CERMAV-CNRS
CY  - Grenoble, France
KW  - Pseudomonas aeruginosa
KW  - lectin
KW  - microcalorimetry
KW  - crystal structure
KW  - cystic fibrosis
N2  - The galactose- and fucose-binding (PA-IL and PA-IIL) lectins of Pseudomonas aeruginosa contribute to the virulence of this pathogenic bacterium, which is a major cause of morbidity and mortality in cystic fibrosis (CF) patients via chronic lung colonisation. CF gene mutations increase cell surface fucosylation and CF patients also display modifications in their respiratory and salivary mucins with a higher percentage of sialylated and sulphated oligosaccharides. These cystic fibrosis mucins and cell surface glycoconjugates carry fucose as the terminal sugar residue. Since the P. aeruginosa lectins have been characterised to reveal an outstandingly high affinity of PA-IIL for fucose, they can serve as binding targets for binding by PA-IIL [1]. Precise three-dimensional knowledge of the lectin sugar binding site, through protein crystallography at high resolution, has allowed the unusually high affinity to be understood and shown a novel sugar binding mode. Subsequent modelling studies, based on the fucose complex structure, and binding studies have demonstrated that the preferred ligands of this bacterial lectin belong to the Lea series. Such structure-based knowledge could be used for the design of efficient anti-bacterial compounds and, furthermore, the unusually high affinity interaction of this novel binding mode suggests that PA-IIL may be a useful target for oligosaccharide-based therapeutics.
ER  -

MITCHELL, Edward; Corrine HOULES; Charles SABIN; Michaela WIMMEROVÁ; Catherine GAUTIER; Serge PEREZ; Albert M. WU; Nechama GILBOA-GARBER and Anne IMBERTY. Structural basis for oligosaccharide-mediated adhesion of P. aeruginosa in the lungs of cystic fibrosis patients. In \textit{12th European Carbohydrate Symposium}. Grenoble, France: CERMAV-CNRS, 2003, p.~61.

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