Quorum sensing (QS) is a widespread bacterial communication system based on the secretion and perception of specific signal molecules allowing single bacterial cells to coordinate gene expression in response to cell-density and environmental cues.
The Gram-negative bacterium Pseudomonas aeruginosa causes various types of severe infections in hospitalized patients and lethal lung infections in cystic fibrosis patients, and it is included in the multidrug resistant ESKAPE group of pathogens.
P. aeruginosa has become a major model organism for studies concerning QS, with the first paper published in 1994 and an average of about 300 publications per year from 2013 to date. The interest of the scientific community about P. aeruginosa QS can be explained by the fascinating complexity of this communication system and by its potential as a drug target. In fact, P. aeruginosa QS is based on multiple signal molecules and cognate receptors intertwined in the global cell regulatory network. This confers an amazing phenotypic plasticity allowing adaptation to a variety of challenging environmental niches and reflecting P. aeruginosa ability to produce a variety of infection types.
This talk will retrace the research about P. aeruginosa QS carried out by our group along almost two decades, from the characterization of basic molecular mechanisms contributing to the QS regulatory network and phenotypic plasticity, to the development of synthetic biology tools for anti-virulence drug discovery and liposome-based therapies. By giving solid examples of successes and bottlenecks, this excursus will hopefully help understand why, despites the efforts of the scientific community, the knowledge about P. aeruginosa QS is still elusive, and no antivirulence drug targeting QS has entered into clinical trials so far.