Different Conformations Revealed by NMR Underlie Resistance to Ceftazidime/Avibactam and Susceptibility to Meropenem and Imipenem among D179Y Variants of KPC β-Lactamase
Magdalena A. Taracila, Christopher R. Bethel, Andrea M. Hujer, Krisztina M. Papp‐Wallace, Melissa D. Barnes, Joseph Rutter, Jamie VanPelt, Ben A. Shurina, Focco van den Akker, Cornelius J. Clancy, M. Hong Nguyen, Shaoji Cheng, Ryan K. Shields, Richard C. Page, Robert A. Bonomo
Abstract
β-Lactamase-mediated resistance to ceftazidime-avibactam (CZA) is a serious limitation in the treatment of Gram-negative bacteria harboring Klebsiella pneumoniae carbapenemase (KPC). Herein, the basis of susceptibility to carbapenems and resistance to ceftazidime (CAZ) and CZA of the D179Y variant of KPC-2 and -3 was explored. First, we determined that resistance to CZA in a laboratory strain of Escherichia coli DH10B was not due to increased expression levels of the variant enzymes, as demonstrated by reverse transcription PCR (RT-PCR).