A new generation of B-lactamase inhibitors is likely to reach the market in the upcoming year. These broad-spectrum inhibitors exhibit activity against the most feared class B metallo-B-lactamases maintaining the inhibition of other enzymes. Recently AAC has published three papers that describe the mechanistic bases of taniborbactam resistance among metallo-enzymes. This knowledge is crucial to understand the limitation of these compounds in clinical practice. Today, we will discuss this topic with some of the authors of the mentioned papers. Welcome to the editors in conversation.
Topics discussed:
- The activity and chemical basis of new generation B-lactamase inhibitors with activity against metallo-B-lactamases.
- Taniborbactam as an example of novel B-lactam, B-lactam inhibitors
- Mechanisms of resistance to taniborbactam and other inhibitors
Guests:
- Robert Bonomo, MD. Director of the VA CARES Center and Distinguished Professor at Case Western Reserve University (CWRU) School of Medicine. Past Editor of AAC
- Pranita Tamma, MD MPH. Associate Professor of Pediatrics, Johns Hopkins School of Medicine, Editor of AAC
- Alejandro Vila, PhD Professor of Biophysics, Instituto de Biologia Molecular y Celular de Rosario, CONICET - Universidad Nacional de Rosario, Rosario, Argentina
Links:
- “The metallo-β-lactamases strike back: emergence of taniborbactam escape variants,” Pranita D. Tamma, Jose M. Munita
- “Structural role of K224 in taniborbactam inhibition of NDM-1,” Daisuke Ono, Maria F. Mojica, Christopher R. Bethel, Yoshikazu Ishii, Salvador I. Drusin, Diego M. Moreno, Alejandro J. Vila, Robert A. Bonomo
- “Relative inhibitory activities of the broad-spectrum β-lactamase inhibitor taniborbactam against metallo-β-lactamases,” Christophe Le Terrier, Clément Viguier, Patrice Nordmann, Alejandro J. Vila, Laurent Poirel
- “Structural basis of metallo-β-lactamase resistance to taniborbactam,” Salvador I. Drusin, Christophe Le Terrier, Laurent Poirel, Robert A. Bonomo, Alejandro J. Vila, Diego M. Moreno
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