Modified Galacto- or Fuco-Clusters Exploiting the Siderophore Pathway to Inhibit the LecA- or LecB-Associated Virulence of Pseudomonas aeruginosa.

Autor: Madaoui M; Institut des Biomolécules Max Mousseron (IBMM), Université Montpellier, CNRS, ENSCM, Montpellier, France., Vidal O; Unité de Glycobiologie Structurelle et Fonctionnelle (UGSF), UMR 8576 CNRS, Université de Lille Cité Scientifique, Avenue Mendeleiev, Bat. C9, 59655, Villeneuve d'Ascq Cedex, France., Meyer A; Institut des Biomolécules Max Mousseron (IBMM), Université Montpellier, CNRS, ENSCM, Montpellier, France., Noël M; Institut des Biomolécules Max Mousseron (IBMM), Université Montpellier, CNRS, ENSCM, Montpellier, France., Lacroix JM; Unité de Glycobiologie Structurelle et Fonctionnelle (UGSF), UMR 8576 CNRS, Université de Lille Cité Scientifique, Avenue Mendeleiev, Bat. C9, 59655, Villeneuve d'Ascq Cedex, France., Vasseur JJ; Institut des Biomolécules Max Mousseron (IBMM), Université Montpellier, CNRS, ENSCM, Montpellier, France., Marra A; Institut des Biomolécules Max Mousseron (IBMM), Université Montpellier, CNRS, ENSCM, Montpellier, France., Morvan F; Institut des Biomolécules Max Mousseron (IBMM), Université Montpellier, CNRS, ENSCM, Montpellier, France.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2020 Dec 01; Vol. 21 (23), pp. 3433-3448. Date of Electronic Publication: 2020 Aug 31.
DOI: 10.1002/cbic.202000490
Abstrakt: Galacto- and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesised to target LecA and LecB lectins of Pseudomonas aeruginosa (PA) localised in the outer membrane and inside the bacterium. The resulting glycocluster-pseudosiderophore conjugates were evaluated as Trojan horses to cross the outer membrane of PA by iron transport. The data suggest that glycoclusters with catechol moieties are able to hijack the iron transport, whereas those with hydroxamates showed strong nonspecific interactions. Mono- and tricatechol galactoclusters (G1C and G3C) were evaluated as inhibitors of infection by PA in comparison with the free galactocluster (G0). All of them exhibited an inhibitory effect between 46 to 75 % at 100 μM, with a higher potency than G0. This result shows that LecA localised in the outer membrane of PA is involved in the infection mechanism.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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