β-Lactamases- The threat renews

β-Lactamases are the greatest single source of resistance to β-lactam antibiotics. For over 60 years, clinicians have seen a pattern whereby useful new β-lactam analogues are introduced but then select for new β-lactamases that cause resistance. Thus, penicillin G was undermined by swift accumulation of staphylococcal penicillinase, ampicillin by TEM-1 enzyme and modern oxymino cephalosporins by "extended-spectrum" β-lactamases. Tony Fink's work contributed greatly to our understanding of the mechanisms and active site function of β-lactamases and this knowledge now informs the search for new β-lactams and β-lactamase inhibitors.