Ab Initio Raman Spectra of β-Lactamase Inhibitor Intermediates Bound to E166A SHV β-Lactamase.

The assignment and the analysis of the experimental vibrational Raman spectra of enzyme bound β-lactamase inhibitors may be of help to understand the mechanisms responsible for bacterial drug resistance. We present a computational study of the structural and vibrational properties of clavulanic acid and tazobactam intermediates, two important β-lactamase inhibitors, bound to the singly mutated E166A SHV β-lactamase in aqueous solution by hybrid molecular mechanics/quantum mechanics (QM/MM) simulations at ambient conditions. We compare the Raman spectra obtained from the time autocorrelation function of polarizability tensor as obtained from a QM/MM protocol to those obtained from the instantaneous normal modes analysis performed on top of the QM/MM trajectory in order to establish the accuracy of these two computational methods and to review the previously made assignments.

β-lactams against emerging 'superbugs': progress and pitfalls.

Bacterial resistance to antimicrobial agents is an ever-growing problem. So-called 'superbugs', such as multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa harboring multiple resistance determinants, including extended-spectrum β-lactamases, carbapenemases, efflux pumps and downregulated outer-membrane proteins or porins, are becoming more prevalent in hospital, intensive and long-term care settings. Enterobacteriaceae are also acquiring a myriad of β-lactamases, such as class A and D carbapenemases, and plasmid-borne class C cephalosporinases.