Interactions of the fucose-specific Pseudomonas aeruginosa lectin, PA-IIL, with mammalian glycoconjugates bearing polyvalent Lewisa and ABH blood group glycotopes

A. M. Wu, J. H. Wu, T. Singh, J. H. Liu, M. S. Tsai, N. Gilboa-Garber

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47 Scopus citations

Abstract

Pseudomonas aeruginosa Fuc > Man specific lectin, PA-IIL, is an important microbial agglutinin that might be involved in P. aeruginosa infections in humans. In order to delineate the structures of these lectin receptors, its detailed carbohydrate recognition profile was studied both by microtiter plate biotin/avidin-mediated enzyme-lectin-glycan binding assay (ELLSA) and by inhibition of the lectin-glycan interaction. Among 40 glycans tested for binding, PA-IIL reacted well with all human blood group ABH and Lea/Leb active glycoproteins (gps), but weakly or not at all with their precursor gps and N-linked gps. Among the sugar ligands tested by the inhibition assay, the Lea pentasaccharide lacto-N-fucopentaose II (LNFP II, Galβ1-3[Fucα1-4]GlcNAcβ1-3Galβ1-4Glc) was the most potent one, being 10 and 38 times more active than the Lex pentasaccharide (LNFP III, Galβ1-4 [Fucα1-3]GlcNAcβ1-3Galβ1-4Glc) and sialyl Lex (Neu5Acα2-3Galβ1-4[Fucα1-3] GlcNAc), respectively. It was 120 times more active than Man, while Gal and GalNAc were inactive. The decreasing order of PA-IIL affinity for the oligosaccharides tested was: Lea pentaose ≥ sialyl Lea tetraose > methyl αFuc > Fuc and Fucα1-2Gal (H disaccharide) > 2′-fucosyllactose (H trisaccharide), Lex pentaose, Leb hexaose (LNDFH I) and gluco-analogue of Ley tetraose (LDFT) > H type I determinant (LNFP I) > Lex trisaccharide (Galβ1-4[Fucα1-3]GlcNAc) > sialyl Lex trisaccharide >> Man >>> Gal, GalNAc, and Glc (inactive). The results presented here, in accordance with the crystal 3D structural data, imply that the combining site of PA-IIL is a small cavity-type best fitting Fucα1- with a specific shallow groove subsite for the remainder part of the Lea saccharides, and that polyvalent glycotopes enhance the reactivity. The Fuc > Man Ralstonia solanacearum lectin RSL, which resembles PA-IIL in sugar specificity, differs from it in it's better fit to the B and A followed by H oligosaccharides vs. Fuc, whereas, the second R. solanacearum lectin RS-IIL (the structural homologue of PA-IIL) binds Man > Fuc. These results provide a valuable information on PA-IIL interactions with mammalian glycoforms and the possible spectrum of attachment sites for the homing of this aggressive bacterium onto the target molecules. Such information might be useful for the antiadhesive therapy of P. aeruginosa infections.

Original languageEnglish
Pages (from-to)1479-1492
Number of pages14
JournalBiochimie
Volume88
Issue number10
DOIs
StatePublished - Oct 2006

Bibliographical note

Funding Information:
This work was supported by grants from the Chang-Gung Medical Research Project (CMRP No. 1028), Kwei San, Tao Yuan, Taiwan, the National Science Council (NSC 91-2311-B-182-004, 91-2320-B-182-032 and 91-2320-B-182-023), Taipei, Taiwan, and by Bar-Ilan Research Fund, Ramat Gan, Israel.

Keywords

  • Bacterial lectin
  • Binding properties
  • Combining sites
  • Glycoproteins
  • Pseudomonas aeruginosa

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