Updated functional classification of β-lactamases. This classic paper correlates the molecular and functional classification schemes of β-lactamases, augmenting the Ambler classes.īush, K. A functional classification scheme for β-lactamases and its correlation with molecular structure. This article is the original paper outlining the molecular classification of β-lactamases.īush, K., Jacoby, G. This paper provides a description of the first BLI that was developed as a commercial product.Īmbler, R. Clavulanic acid: a beta-lactamase-inhiting beta-lactam from Streptomyces clavuligerus. Past and present perspectives on β-lactamases. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Resistance of Staphylococcus aureus to the action of penicillin. Metallo-β-lactamase structure and function. Extended-spectrum and inhibitor-resistant TEM-type β-lactamases: mutations, specificity, and three-dimensional structure. Penicillin-binding proteins of gram-negative bacteria. Penicillins and cephalosporins are active site-directed acylating agents: evidence in support of the substrate analogue hypothesis.
& Bush, K.) 23–44 (Cold Spring Harbor Laboratory Press, 2016). in Antibiotics and Antibiotic Resistance (eds Silver, L. Recently approved inhibitor combinations include the inhibitors avibactam and vaborbactam of the diazabicyclooctanone and boronic acid inhibitor classes, respectively, as new scaffolds for future inhibitor design.īush, K.
In this Review, descriptions are provided for medically relevant β-lactamase families and various BLI combinations that have been developed or are under development. However, some β-lactam–BLI combinations have lost their effectiveness against prevalent Gram-negative pathogens that produce ESBLs, carbapenemases or multiple β-lactamases in the same organism. To counteract the hydrolytic activity of these enzymes, combinations of a β-lactam with a β-lactamase inhibitor (BLI) have been clinically successful. Resistance to β-lactam antibiotics in Gram-negative bacteria is commonly associated with production of β-lactamases, including extended-spectrum β-lactamases (ESBLs) and carbapenemases belonging to different molecular classes: those with a catalytically active serine and those with at least one active-site Zn 2+ to facilitate hydrolysis.
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