3-Aminooxazolidinone AHL analogs as hydrolytically-stable quorum sensing agonists in Gram-negative bacteria

Synthetic molecules that modulate quorum sensing, QS, in bacteria have great potential for use in synthetic biology applications as well as acting as anti-virulence and anti-biofilm agents. Acylhomoserine lactone (AHL)-based autoinducer analogs have been extensively developed as QS modulators but these suffer from both chemical and enzymatic degradations. Here, we reveal that 3-aminooxazolidinone acylhomoserine lactone analogs are hydrolytically stable and are as potent in activating LuxR-type receptors. Docking analysis revealed that 3-oxo-C12-3-aminooxazolidinone docked in LasR of P. aeruginosa, making similar interactions with the protein's active-site residues to the native ligand, 3-oxo-C12 HSL. Experimentally, 3-oxo-C12-3-aminooxazolidinone was equally as potent as the natural ligand in inducing bioluminescence in E. coli carrying a bioluminescent gene that was under the control of LasR. In C. violaceum CV026, the 3-aminooxazolidinone analogs could also modulate pigment (violacein) formation, albeit this time not as potent as the natural AHL ligands.