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Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
Published on: June 30, 2016
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High-Throughput Screening for Compounds that Modulate the Cellular c-di-GMP Level in Bacteria
Julie Groizeleau1, Jens Bo Andersen1, Michael Givskov1,2
1Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Methods in Molecular Biology (Clifton, N.J.)
|September 11, 2017
Summary
New drugs targeting bacterial biofilms are needed. This study presents a high-throughput screening method to identify compounds that reduce cyclic di-GMP (c-di-GMP) levels, potentially making biofilm bacteria more susceptible to treatment.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Drug Discovery
Background:
- Bacterial biofilms are highly resistant to antibiotics and host immune responses, leading to persistent and difficult-to-treat infections.
- Conventional antimicrobial agents are often ineffective against bacteria in the biofilm growth mode.
- The secondary messenger cyclic di-GMP (c-di-GMP) is a key regulator promoting biofilm formation in many bacterial species.
Purpose of the Study:
- To develop a high-throughput screening (HTS) protocol to identify novel compounds that reduce intracellular c-di-GMP levels in bacteria.
- To find potential lead compounds for the development of new anti-biofilm therapies.
Main Methods:
- Establishment of a HTS assay to measure bacterial intracellular c-di-GMP levels.
- Screening of diverse chemical libraries against bacterial targets modulating c-di-GMP.
Main Results:
- Successful implementation of a HTS protocol for identifying modulators of bacterial c-di-GMP.
- Identification of compounds that effectively lower c-di-GMP levels in bacteria.
Conclusions:
- Reducing intracellular c-di-GMP levels is a promising strategy to combat biofilm infections.
- The developed HTS protocol can accelerate the discovery of novel anti-biofilm agents.
- Identified compounds serve as starting points for developing drugs to dismantle bacterial biofilms.
