Towards a mechanistic understanding quorum sensing antagonism
The Blackwell research group focuses primarily on identifying small molecules and chemical strategies that interfere in cell-to-cell communication systems found in many common bacterial pathogens. These pathogens use chemical signals to coordinate group behaviors through a process called quorum sensing (QS). In Gramnegative bacteria, a QS system typically includes a LuxI-type synthase that produce an N-acyl L-homoserine lactone (AHL) and a LuxR-type transcription factor that binds the AHL signal and alters its activity. Extensive efforts have been undertaken to identify potent small molecule agonists and antagonists of this class of receptor proteins. However, because most of these receptors are unstable in vitro and in cells in the absence of their native AHL, a dearth of biochemical and biophysical data exists concerning how these ligands modulate these receptors. Elucidating the biophysical effects of small molecules on LuxR-type receptor
activity has been the primary focus of my Ph.D. thesis work in the Blackwell laboratory. I have pursued two general strategies: 1) identifying small molecules that modulate SdiA, a biophysically tractable LuxR-type receptor, and 2) developing chemical probes to allow the interrogation of less tractable, but highly studied LuxR-type receptors.