tetronic-acid and Staphylococcal-Infections

A series of 3-oxo-C12-HSL, tetramic acid, and tetronic acid analogues were synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were noncompetitive inhibitors of the autoinducing peptide (AIP) activated AgrC receptor, by altering the activation efficacy of the cognate AIP-1. They appeared to act as negative allosteric modulators and are exemplified by 3-tetradecanoyltetronic acid 17, which reduced nasal cell colonization and arthritis in a murine infection model.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Cell Line; Furans; Indicators and Reagents; Iron Chelating Agents; Mice; Microbial Sensitivity Tests; Nasal Cavity; Peptides, Cyclic; Protein Kinases; Pyrrolidinones; Quorum Sensing; Signal Transduction; Small Molecule Libraries; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship