SENSING CIRCUITRY TO QUENCH BACTERIAL COMMUNICATION NETWORKS

The emergence of antibiotic resistant bacteria poses a global threat to human health and has been classified as a clinical super-challenge of the 21st century. This has necessitated research on new antimicrobials that inhibit bacterial virulence by mechanisms other than those that target bacterial growth or viability. Such approaches have been reported to pose less evolutionary pressure on bacteria to evolve and become resistant to antibiotics. Bacterial cell-cell communication, termed quorum sensing (QS), is mediated by signatures of small molecules. QS via these small molecules has been linked to numerous undesirable bacterial phenotypes such as biofilm formation, onset of pathogenicity, triggering of virulence genes etc. The small signaling molecules represent targets for intercepting bacterial communication (and their resultant undesirable phenotypes). We have devised two strategies that interrupt bacterial communication in multispecies bacterial cultures by targeting the interspecies signaling molecule autoinducer-2 (AI-2), which is produced or recognized by over 70 species of bacteria. Our first approach is to bring the native intracellular AI-2 signal processing mechanisms to the extracellular surroundings t