Targeting c-di-GMP Signaling, Biofilm Formation, and Bacterial Motility with Small Molecules

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 1657)

Abstract

Bacteria possess several signaling molecules that regulate distinct phenotypes. Cyclic di-GMP (c-di-GMP) has emerged as a ubiquitous second messenger that regulates bacterial virulence, cell cycle, motility, and biofilm formation. The link between c-di-GMP signaling and biofilm formation affords novel strategies for treatment of biofilm-associated infections, which is a major public health problem. The complex c-di-GMP signaling pathway creates a hurdle in the development of small molecule modulators. Nonetheless, some progress has been made in this regard and inhibitors of c-di-GMP metabolizing enzymes that affect biofilm formation and motility have been documented. Herein we discuss the components of c-di-GMP signaling, their correlation with biofilm formation as well as motility and reported small molecule inhibitors of c-di-GMP signaling.

Key words

c-di-GMP Diguanylate cyclase Phosphodiesterase PilZ STING Inhibitor 
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Notes

Acknowledgment

We acknowledge funding from the NSF: CHE-1307218 and CHE-1636752.

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© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Purdue Institute for Drug DiscoveryPurdue UniversityWest LafayetteUSA
  2. 2.Department of ChemistryPurdue UniversityWest LafayetteUSA
  3. 3.Biochemistry Graduate ProgramUniversity of MarylandCollege ParkUSA
  4. 4.Purdue Institute of Inflammation, Immunology and Infectious DiseaseWest LafayetteUSA
  5. 5.Department of Chemistry, Center for Drug DiscoveryPurdue UniversityWest LafayetteUSA

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