Effects of the Selected Iminosugar Derivatives on Pseudomonas aeruginosa Biofilm Formation

Microb Drug Resist. 2016 Dec;22(8):638-645. doi: 10.1089/mdr.2015.0231. Epub 2016 Mar 31.

Abstract

A lack of an effective way to eliminate pathogenic bacteria hidden in the biofilm is a major problem in the treatment of chronic bacterial infections. Iminosugar derivatives are potential candidates for inhibitors of enzymes taking part in the biosynthesis of exopolysaccharides, which are forming bacterial biofilm. Investigated iminosugars were studied either at an early stage of biofilm formation or later on when the mature biofilm of Pseudomonas aeruginosa was already formed. A series of diverse iminosugar structures significantly inhibited biofilm formation, whereas they showed no influence on already formed biofilm. This indicates a possible mechanism of their action based on inhibition of exopolysaccharide backbone synthesis in the early stages of biofilm formation. Moreover, iminosugar derivatives did not show significant effect on the viable bacterial numbers in both early and mature biofilm forms. Importantly, they were not cytotoxic against human Caco-2 cells in vitro, which may be to their advantage in case of their medical application in preventing P. aeruginosa biofilm formation.

Keywords: Pseudomonas aeruginosa; biofilm; iminosugars.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Colony Count, Microbial
  • Humans
  • Imino Sugars / chemistry
  • Imino Sugars / pharmacology*
  • Microbial Viability / drug effects
  • Polysaccharides, Bacterial / antagonists & inhibitors*
  • Polysaccharides, Bacterial / biosynthesis
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism
  • Species Specificity
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Imino Sugars
  • Polysaccharides, Bacterial