Award
National Institute of Allergy and Infectious Diseases 1R01AI197205-01
Time resolved structural analyses of -lactam/-lactam inhibitor binding to AmpC
Recipient
University of Pittsburgh at Pittsburgh
Award Amount
$799,572.00
Ceiling
$799,572.00
Awarded
April 01, 2026
Identifier
1R01AI197205-01
This NIH-funded research project aims to use time-resolved crystallography and other methods to study how AmpC -lactamase interacts with -lactam antibiotics and inhibitors, to inform development of better treatments against resistant bacteria.
Description
The goal of this study is to apply time-resolved crystallography, coupled with biochemical and microbiological approaches, to understand how the AmpC -lactamase binds and metabolizes -lactam antibiotics and -lactamase inhibitors (BLIs), and how mutations in extended-spectrum AmpCs enhance their catalytic efficiency toward cephalosporins while decreasing inhibition by BLIs. These insights aim to aid in developing more effective -lactam antibiotics and BLIs, crucial in combating antibiotic-resistant gram-negative bacteria.