Abstract:

New Delhi Metallo-β-lactamase (NDM) grants resistance to a broad spectrum of β-lactam antibiotics including last-resort carbapenems and is emerging as a global antibiotic resistance threat. Limited zinc availability adversely impacts the ability of NDM-1 to provide resistance, but a number of clinical variants have emerged that are more resistant to zinc scarcity. To provide novel tools to better study metal ion sequestration in host-pathogen interactions and the dynamic metalation state of NDM in these contexts, we are developing fluorescent probes that bind to the dizinc of active site of NDM. The development of reversible turn-on fluorescent probes for the metalation state of NDM provides a means to monitor the impact of metal ion sequestration by host defense mechanisms and to detect inhibitor target engagement during the development of therapeutics to counter this resistance determinant. Recent developments in our lab along this research theme will be discussed.

About the Speaker: 

Prof. Que received her B.S. in Chemistry from the University of Minnesota. She continued on the pursue her Ph.D. in chemistry in Prof. Chris Chang’s lab at the University of California Berkeley, where she developed metal-responsive MRI contrast agents. She then moved to Northwestern University to work with Profs. Tom O’Halloran and Teresa Woodruff on understanding the roles of zinc uring mammalian fertilization. She began her independent career at the University of Texas at Austin in 2014 and was awarded tenure in 2021. Her research in the development of new bioinorganic imaging tools including metalloenzyme sensors and MRI contrast agents has been recognized via the Saltman lectureship at the Metals in Biology Gordon research conference, an Emerging Investigator award from the Molecular Sensors and Molecular Logic Gates conference, and NSF CAREER and NIH MIRA grants.