Development of inhibitors of bacterial flap endonucleases for use as antimicrobial agents

The development and spread of antimicrobial resistance is a complex issue to which the costs of inaction are huge. Today, 700,000 people die of resistant infections every year and it is estimated that by 2050, 10 million lives a year are at risk due to the rise of drug-resistant infections. Additionally, it has been shown that the antibiotics that have been recently approved, and those at various stages of development, show a mismatch between what the world needs, given emerging levels of drug resistance, and the size and quality of the pipeline to address this growing challenge. In particular, there is a critical need for new classes of antibiotics, acting via novel biological pathways. Bacterial flap endonucleases (FENs) are highly conserved enzymes that are essential for DNA replication and repair and the maintenance of genomic stability in pathogenic bacteria. Since loss of FEN activity is fatal to the target organism, they represent a new class of target for the development of novel, high-value antibiotics with a low resistance profile. This project, undertaken by DeFENition Ltd, a newly formed biotech, in partnership with the Sheffield University, is aiming at identifying and developing bacterial FENs inhibitors for use as antibiotic agents.