Synthetic small molecules as anti-biofilm agents in the struggle against antibiotic resistance

Eur J Med Chem. 2019 Jan 1:161:154-178. doi: 10.1016/j.ejmech.2018.10.036. Epub 2018 Oct 17.

Abstract

Biofilm formation significantly contributes to microbial survival in hostile environments and it is currently considered a key virulence factor for pathogens responsible for serious chronic infections. In the last decade many efforts have been made to identify new agents able to modulate bacterial biofilm life cycle, and many compounds have shown interesting activities in inhibiting biofilm formation or in dispersing pre-formed biofilms. However, only a few of these compounds were tested using in vivo models for their clinical significance. Contrary to conventional antibiotics, most of the anti-biofilm compounds act as anti-virulence agents as they do not affect bacterial growth. In this review we selected the most relevant literature of the last decade, focusing on the development of synthetic small molecules able to prevent bacterial biofilm formation or to eradicate pre-existing biofilms of clinically relevant Gram-positive and Gram-negative pathogens. In addition, we provide a comprehensive list of the possible targets to counteract biofilm formation and development, as well as a detailed discussion the advantages and disadvantages of the different current biofilm-targeting strategies.

Keywords: Anti-adhesion agents; Anti-biofilm agents; Anti-virulence compounds; Antibiotic resistance; Dispersal agents.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Biofilms / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Microbial / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Small Molecule Libraries