Detecting the Changes Caused by Activators and Inhibitors in a Key Protein for Bacterial Virulence
In a research article recently published in the prestigious journal ACS Nano, researchers from the group of Prof. Luis M. Liz-Marzan in the CIC biomaGUNE and the University of Vigo with the collaboration of Prof. Concepción González-Bello in the CIQUS, detect the changes caused by small molecules in a key protein involved in cell-to-cell communication, which is also known as Quorum Sensing (QS). As many other proteins, it follows the key and lock model, which means that the protein is only activated by the right molecule. As a consequence, the protein adopts the active conformation that triggers important pathogenic processes. The discovery that bacteria are able to communicate with each other to regulate important cellular processes had changed our general perception of them as single and simple organisms inhabiting our world.
Instead of language, bacteria use signalling small diffusible molecules (autoinducers) that are released into the environment. As the number of cells in a bacterial colony increases, so does the extracellular concentration of the autoinducer. Once a threshold concentration (quorum) is reached, a signal transduction cascade is triggered including virulence, antibiotic resistance and biofilm formation, which all play a critical role in bacterial pathogenicity. This bacterial cell-to-cell communication system that relies in the activation of receptor proteins by small molecules is a recognized attractive target for the development of anti-virulence agents (inhibitors) to combat widespread antibiotic resistance, which has become one of the most important public health issues of the early 21st century.
The results reported in this article provide detailed knowledge of the binding determinants of the receptor protein to autoinducers (activators) or inhibitors, as well as the conformational changes caused by those molecules.
These findings would be an excellent starting point for design of novel anti-virulence drug avoiding the active conformation of this important protein. QS is a relevant target for anti-virulence therapy because it controls virulence gene expression in many bacterial pathogens such as Pseudomonas aeruginosa, which is the most common pathogen in hospitals.