Emergence and characterization of lipidated β-lactamases

Since the discovery of penicillin, β-lactam antibiotics have been a mainstay for the treatment of bacterial infections. Resistance to β-lactam antibiotics via β-lactamase enzymes was identified before β-lactams even reached a clinical setting, and decades of use has only increased the risk posed by β-lactam resistance, largely driven by β-lactamase enzymes. While most β-lactamases are soluble periplasmic enzymes, a minority are membrane anchored lipoproteins. With the emergence and proliferation of the highly potent New Delhi metallo-β-lactamase (NDM) in the late 2000's, lipidated β-lactamases have catapulted from little more than biochemical curiosities, to key features of one of the most potent and prevalent antibiotic resistance enzymes. NDM is the most well-known lipidated β-lactamase. However, recent work highlights both emerging lipidated β-lactamases as well as the fact that lipidation may be more common in previously characterized β-lactamases than thought.