Since the introduction of penicillin, β-lactam antibiotics have been the antimicrobial agents
of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened …

The most common mechanism of resistance to β-lactam antibiotics in Gram-negative
bacteria is the production of β-lactamases that hydrolyze the drugs. Class A β-lactamases …

TEM-1 β-lactamase is one of the most well-known antibiotic resistance determinants around.
It confers resistance to penicillins and early cephalosporins and has shown an astonishing …

β-Lactamases are the main cause of bacterial resistance to penicillins, cephalosporins and
related β-lactam compounds. These enzymes inactivate the antibiotics by hydrolysing the …

In the last decade the usefulness of the oximino-β-lactams and monobactams has been
compromised by the increasing presence of clinically derived extended-spectrum β …

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves
activity against new drugs. However, functional changes are not easily explained by …

Protein evolvability includes two elements—robustness (or neutrality, mutations having no
effect) and innovability (mutations readily inducing new functions). How are these two …

For a number of years a major limitation in genetic analysis of protein function has been the
inability to introduce multiple substitutions at distant sites that would enable the selection of …

Epistasis is a key factor in evolution since it determines which combinations of mutations
provide adaptive solutions and which mutational pathways toward these solutions are …

The spread of β-lactamases that hydrolyze penicillins, cephalosporins and carbapenems
among Gram-negative bacteria has limited options for treating bacterial infections. Initially …