β-Lactamases and β-Lactamase Inhibitors in the 21st Century

The β-lactams retain a central place in the antibacterial armamentarium. In Gram-negative bacteria, β-lactamase enzymes that hydrolyze the amide bond of the four-membered β-lactam ring are the primary resistance mechanism, with multiple enzymes disseminating on mobile genetic elements across opportunistic pathogens such as Enterobacteriaceae (e.g., Escherichia coli) and non-fermenting organisms (e.g., Pseudomonas aeruginosa). β-Lactamases divide into four classes; the active-site serine β-lactamases (classes A, C and D) and the zinc-dependent or metallo-β-lactamases (MBLs; class B). Here we review recent advances in mechanistic understanding of each class, focusing upon how growing numbers of crystal…

• NI
  National Institutes of Health

  Award: R01AI100560
• DF
  Directorate for Biological Sciences
• MR
  Medical Research Council

  Awards: MR/N0137941/1, 1952779, GW4 BIOMED DTP, MR/N0137941
• BA
  Biotechnology and Biological Sciences Research Council

  Award: 1648380
• NI
  National Institute of Allergy and Infectious Diseases

  Award: R01AI100560