Novel approaches for the design and discovery of quorum-sensing inhibitors

The spread of antibiotic resistance, together with the lack of antibiotics based on novel molecular scaffolds, marks the so-called 'post-antibiotic era'. Interference with bacterial virulence has emerged as an attractive approach among the current potential strategies for developing new anti-infective drugs. Furthermore, the discovery that virulence gene expression is mostly regulated by quorum sensing (QS) has raised a lot of interest and prompted a lot of research aimed at finding inhibitors of this mechanism.

This paper deals with the most recent strategies aimed at discovering new inhibitors able to disrupt the different steps of the QS system, targeting signal production, signal molecules and signal receptors. The authors provide an overview of the literature, including research papers, mostly dealing with inhibitors of the Staphylococcus aureus and Pseudomonas aeruginosa QS systems, and reviews dealing with the application of the newest technologies in the field. They also highlight the field's latest prospects and emerging concerns regarding their possible clinical applications.

QS inhibition is a promising strategy against infections. However, despite the discovery of a huge number of QS inhibitors, with about 40 patents, the potential of QS inhibition is still to be fully assessed. The current validation methods of QS inhibitors must be optimized, and the discovery that QS disruption may favor or select more virulent strains must be investigated in depth. Given the current market-dependent situation, it should be possible to develop hits into licensed drugs through joint ventures between private companies, academia and public institutions.