Bacterial resistance to �-lactam containing antibiotics (penicillins and carbapenems) is an enormous biomedical problem, which costs billions of dollars each year.  Carbapenems are often prescribed for the treatment of hospital-acquired infections in patients that have already been exposed to other antibiotic regiments. Recently, community-acquired E. coli and K. pneumoniae strains have emerged that are resistant to carbapenems, due to their production of N ew D elhi M etallo-�-lactamase (NDM-1). NDM-1 is an enzyme that binds to and inactivates carbapenems. The goal of our research is to design and prepare small chemical compounds that inhibit the catalytic activity of NDM-1; these compounds would be called inhibitors. We aimed to achieve this goal by purifying large quantities of NDM-1 and characterizing the enzyme using several biochemical techniques. We performed enzyme kinetic studies using a series of related cephalosporins, and we identified a potential strategy to inhibit NDM-1.

Inhibition studies on metallo-�-lactamase NDM-1

247th National Meeting (2014)

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