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

Chembiochem. 2020 Dec 1;21(23):3433-3448. doi: 10.1002/cbic.202000490. Epub 2020 Aug 31.

Abstract

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.

Keywords: Pseudomonas aeruginosa; glycoclusters; iron transport; lectins; siderophores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / metabolism*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Fucose / chemical synthesis
  • Fucose / chemistry
  • Fucose / pharmacology
  • Galactose / chemical synthesis
  • Galactose / chemistry
  • Galactose / pharmacology
  • Lectins / antagonists & inhibitors*
  • Lectins / metabolism
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / metabolism
  • Pseudomonas aeruginosa / pathogenicity
  • Siderophores / chemistry
  • Siderophores / pharmacology
  • Virulence

Substances

  • Adhesins, Bacterial
  • Anti-Bacterial Agents
  • LecA protein, bacteria
  • LecB protein, Pseudomonas aeruginosa
  • Lectins
  • Siderophores
  • Fucose
  • Galactose