Affimer Inhibition of Verona Integron-encoded Metallo-β-Lactamase 1

Metallo-β-lactamases (MBLs) are a class of enzyme that hydrolyse the β-lactam ring in β-lactam antibiotics through their active site Zn2+ rendering them inactive. Verona Integron-encoded metallo-β-lactamase 1 (VIM-1) is a class B1, group 3, carbapenemase which is easily disseminated through the plasmid blaVIM, and offers bacteria broad-spectrum resistance to almost all known β-lactam antibiotics. A combination of β-lactamase inhibitors with β-lactam antibiotics is currently the most reliable method of dealing with resistant pathogens, but there are currently no clinically available inhibitors of this class of MBL.

Affimers, a class of non-antibody binding proteins could potentially offer an alternative source of novel MBL inhibitors. An Affimer that binds and inhibits New Delhi metallo-β-lactamase (NDM-1), a structurally similar MBL to VIM-1, has previously been identified. It was proposed that utilising similar screening methods, Affimer reagents could be raised against VIM-1 also to bind and modulate its activity. Though further study is needed, as a result of this work, an Affimer (Affimer61) was identified that was capable of reducing VIM-1’s hydrolysis of nitrocefin substrate by 47%.