Strategies and Approaches for Discovery of Small Molecule Disruptors of Biofilm Physiology

Molecules. 2021 Jul 29;26(15):4582. doi: 10.3390/molecules26154582.

Abstract

Biofilms, the predominant growth mode of microorganisms, pose a significant risk to human health. The protective biofilm matrix, typically composed of exopolysaccharides, proteins, nucleic acids, and lipids, combined with biofilm-grown bacteria's heterogenous physiology, leads to enhanced fitness and tolerance to traditional methods for treatment. There is a need to identify biofilm inhibitors using diverse approaches and targeting different stages of biofilm formation. This review discusses discovery strategies that successfully identified a wide range of inhibitors and the processes used to characterize their inhibition mechanism and further improvement. Additionally, we examine the structure-activity relationship (SAR) for some of these inhibitors to optimize inhibitor activity.

Keywords: biofilm inhibitors; biofilms; c-di-GMP inhibitors; inhibitor discovery; structure-activity relationship.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Cyclic GMP / antagonists & inhibitors
  • Cyclic GMP / chemistry
  • Cyclic GMP / metabolism
  • Drug Design
  • Drug Discovery
  • Drug Resistance, Bacterial / drug effects
  • Extracellular Polymeric Substance Matrix / chemistry
  • Extracellular Polymeric Substance Matrix / drug effects*
  • Extracellular Polymeric Substance Matrix / metabolism
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / growth & development
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / growth & development
  • Gram-Positive Bacteria / pathogenicity
  • Lipids / antagonists & inhibitors
  • Lipids / chemistry
  • Microbial Sensitivity Tests
  • Nucleic Acids / antagonists & inhibitors
  • Nucleic Acids / chemistry
  • Nucleic Acids / metabolism
  • Polysaccharides, Bacterial / antagonists & inhibitors
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / isolation & purification
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Lipids
  • Nucleic Acids
  • Polysaccharides, Bacterial
  • Small Molecule Libraries
  • Cyclic GMP