beta-Lactamases- the Threat Renews.

Beta-lactamases are the greatest single source of resistance to beta-lactam antibiotics. For over 60 years, clinicians have seen a pattern whereby useful new beta-lactam analogues are introduced but then select for new beta-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" beta-lactamases. Tony Fink's work contributed greatly to our understanding of the mechanisms and active site function of beta-lactamases and this knowledge now informs the search for new beta-lactams and beta-lactamase inhibitors.