|Name||Ms. Afroza Akhtar|
|Organization or Institution||University of South Florida|
|Topic||Biochemistry / Chem Bio.|
Development of Tetrazole based Inhibitors against Multiple Classes of Carbapenemases
Afroza Akhtar, Orville Pemberton, Xiujun Zhang, Yu Chen
University of South Florida
Carbapenemases are the most versatile family of beta lactamases which are capable of hydrolyzing virtually all beta lactam antibiotics including carbapenem, the last resort of treatment in the clinical settings to treat bacterial infection. Previous studies have showed that tetrazole compounds can act as a potent inhibitor against extended spectrum beta lactamase CTX-M. Here we found a tetrazole compound in the active site of KPC-2 (class A carbapenemase), NDM-1(class B carbapenemase) and OXA-48(class D carbapenemase). For all those enzymes, this compound exhibit activity in microM level. This study provides both biochemical and biophysical report to show that tetrazole based inhibitors could be used as a potential scaffold to target different classes of carbapenemases in a non-covalent fashion.