Strategies and approaches for discovery of small molecule disruptors of biofilm physiology

Michael A. Trebino, Rahul D. Shingare, John B. Macmillan, Fitnat H. Yildiz

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Article number4582
JournalMolecules
Volume26
Issue number15
DOIs
StatePublished - Aug 1 2021
Externally publishedYes

Keywords

  • Biofilm inhibitors
  • Biofilms
  • C-di-GMP inhibitors
  • Inhibitor discovery
  • Structure-activity relationship

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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