Understanding the mechanism of action of quorum sensing inhibitors with biophysical methods

Quorum sensing (QS) is a sophisticated communication system that pathogenic bacteria employ to regulate virulence and coordinate group behaviors. The coordinated activation of virulence genes enables bacteria to attack host tissues, evade the immune response, and establish persistent infections. The significance of QS in bacterial virulence underscores its role as a key mediator in the pathogenicity of various infectious agents. The search for QS inhibitors (QSIs) is paramount in microbial control and disease management. By disrupting QS, QSIs have the potential to attenuate bacterial virulence without directly affecting growth, providing a unique strategy to combat bacterial infections. This approach is particularly significant in rising antibiotic resistance, as QSIs offer an alternative route to target pathogens. Understanding QS inhibitory mechanisms presents promising avenues for developing novel antimicrobial strategies that disrupt bacterial communication, attenuate virulence, and potentially mitigate the impact of infectious diseases. In this context, biophysical methods such as surface plasmon resonance, isothermal titration calorimetry, nuclear magnetic resonance, X-ray crystallography, circular dichroism, and fluorescence spectroscopy, among others, offer a comprehensive understanding of protein-ligand interactions providing information about binding kinetics, affinity, and structural details of QSI targets. Therefore, this chapter provides an overview of biophysical methods to characterize the interactions of QSIs and their targets to elucidate their mode of action.