A fundamental property of bacteria adaptation and flexibility is their ability to communicate using chemical signaling, a process called “quorum sensing”. Quorum sensing is linked to many bacterial activities that are important to health, industry and technology, such as antibiotic production, plasmid transfer, virulence in human, animal and plant pathogens, and biofilm formation.

Our studies investigate the exciting and unique chemistry of quorum sensing. We are funded by a four-year project, through the NSF Collaborative Research in Chemistry (CRC) Program. Chemical signaling depends on small diffusible molecules, called ‘autoinducers”.  Acylated homoserine lactones’ (AHLs) are a major class of autoinducers present in gram-negative bacteria, and consist of a lactone ring having an amide-linked acylated side chain varying in length and substitution at the third C position.  It is known that signal specificity stems from subtle differences in the chemical structure of autoinducer molecules and their regulatory protein receptors.  However, chemical signals, once released outside the cell into the extracellular environment, are exposed to a plethora of natural stressors that may potentially alter their chemical structure. These include fluctuations in pH, oxidants, temperature, photocatalytic processes and transition metal concentrations. These alterations have the potential to change signal specificity, the mobility and fate of autoinducers such as AHLs, and efficiency of quorum sensing in natural environments. Quorum sensing, thus, provides a platform for important, fundamental chemistry.

We are addressing four key issues regarding the chemistry of quorum sensing autoinducers (AHLs): (1) How do specific Environmental Stressors modify AHL Molecules?  (2)  How do changes to AHLs alter Complexation to Regulatory Proteins; (3) Which changes in AHL/Protein Binding Result in changes in Gene Expression? (4) Can Raman and fluorescence-lifetime signatures be used to Image/ Quantify in-situ intact and altered AHLs? We are developing multivariate models of AHL hydrolysis, particularly the effects of key environmental variables on the equilibrium constant for the lactone functionality.  The derived models will be used to map out those areas of where more fundamental, molecular explorations of the system are warranted (e.g. the thermodynamics of ring-opening in a non-polar environment). Our investigations employ a range of state-of-the-art approaches (e.g. surface plasmon resonance, Raman-confocal, surface-enhanced Raman using nanoparticles).