Modified Galacto- Or Fuco-Clusters Exploiting The Siderophore Pathway To Inhibit The Leca- Or Lecb-Associated Virulence Ofpseudomonas Aeruginosa

Galacto- and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesised to target LecA and LecB lectins ofPseudomonas 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 (G1CandG3C) 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 mu M, with a higher potency thanG0. This result shows that LecA localised in the outer membrane of PA is involved in the infection mechanism.