Department of Structural Biology and Chemistry
Tuesday 12 november 2019 at 2.00 pm
AUDITORIUM CENTRE F. JACOB room- CFJ RdC 17
Chemistry Research Laboratory – department of Chemistry
University of Oxford – Londres
Enabling antibiotics to combat multidrug resistant bacteria
Global increase in antibiotic resistance causes tens of thousands of deaths each year. Infections by pathogenic Gram-negative bacteria are the most common, with β-lactam antibiotics being the most widely used treatment. The most important type of resistance to them is mediated via β-lactamases. The recent clinical introduction of avibactam and vaborbactam as serine-β-lactamase inhibitors is a major advance. However, the metallo-β-lactamases are of particular concern because they catalyse the hydrolysis of almost all types of β-lactam antibiotics and all serine-β-lactamase (SBL) inhibitors, including avibactam.
Metallo-β-lactamases are particularly challenging targets because of the need to obtain potency against the different clinically relevant subtypes, which differ in the loops surrounding the active sites. The bacterial MBLs belong to the MBL superfamily that up to date includes >30000 members. Bacterial and human MBLs present high active site similarity and high structural similarity. The superfamily contains human MBLs that should not be inhibited by bacterial MBL inhibitors.
In this talk, I will describe the recent work on the mechanisms, structure and inhibition of bacterial metallo and serine-β-lactamases and the impact of my work in the field of antibiotic resistance that has led to the development of a potential drug candidate suitable for clinical development.
Contact : Paola Arimondo
Unité Chimie Biologique Epigénétique