Small molecules that block bacterial communication identified

When pathogenic bacteria like Staphylococcus aureus and Pseudomonas aeruginosa achieve a certain population density, they can communicate via quorum sensing—molecular signals that direct the microbes to act as a group. That communication can have deadly consequences. Researchers at the University of Wisconsin–Madison led by Helen E. Blackwell and David M. Lynn have now developed a method for detecting molecules that block quorum sensing (Cell Chem. Biol. 2021, DOI: 10.1016/j.chembiol.2021.12.005). The assay uses synthetic lipid vesicles—essentially little bubbles—that are loaded with the fluorescent dye calcein. Certain bacteria use quorum sensing to regulate the production of surfactants that can break the vesicles open and release their fluorescent payload. The researchers used the assay to screen a library of more than 25,000 small molecules and found two (shown) that were able to block quorum sensing in S. aureus. The scientists describe the compounds as the most potent small-molecule-derived quorum sensing inhibitors reported in this formidable pathogen. Blackwell says that it’s too early to consider the molecules for clinical use but that they could be employed to explore quorum sensing as a therapeutic target.