Scientists from the Laboratory of Biomolecular Interactions and Transport AMU/IIMCB, led by Jan Brezovsky, Ph.D., have recently published a paper entitled „Common Dynamic Determinants Govern Quorum Quenching Activity in N-Terminal Serine Hydrolases” in ACS Catalysis.

This work addresses alarming global concerns about the rapidly spreading resistance of bacteria against our principal defense, antibiotics. In particular, researchers from Brezovsky’s Lab focused on the process of bacterial communication, called quorum sensing, that enables their social behaviors in an environment-dependent manner. The disruption of this communication through the degradation of the small organic molecules carrying the signal by quorum quenching enzymes was shown to limit the bacterial virulence and resistance markedly. Therefore, the use of these enzymes represents promising alternative for conventional antibiotic therapies

In this paper, researchers prove the quorum quenching activity of two biotechnologically well-known and optimized penicillin G acylases, ecPGA, and aPGA. Additionally, using state-of-the-art computational methods they unveiled dynamic determinants responsible for the relatively low activity of ecPGA and aPGA towards the bacterial signaling molecules. They observed enzyme- and ligand-dependent factors that affect the effectiveness of the initial degradation reaction and that were mainly related to the different dynamics of the gating residues controlling the access to the ligand-binding pockets and the dynamics of these pockets. Considering the high application potential of these enzymes, the discovery of these dynamic determinants will guide future efforts to design robust quorum quenching agents capable of selectively controlling virulence in resistant bacterial species.

The open-access full text of the article can be found here