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Mohammed Al Ali, Getty Images.
In a new study, published recently in the Journal of Medicinal Chemistry, IOI scientists describe new compounds called ‘pyrrole-2-carboxylic acids’ that trap water in bacterial enzymes called metallo-β-lactamases. Metallo-β-lactamases are enzymes that cause resistance in many bacteria, including those responsible for deadly hospital-acquired infections.
In 2023, one in six infections were resistant to antibiotic treatments, reflecting the growing threat of antimicrobial resistance (AMR). AMR occurs when microbes like bacteria, fungi or parasites stop responding to medicines designed to treat them.
Common antibiotics like penicillin are becoming ineffective in treating infections like pneumonia and gonorrhoea, leaving clinicians to rely on vital ‘last-resort’ drugs, often reserved for the most critical patients. Some of these last-resort antibiotics are part of a class called carbapenems.
However, resistant bacteria produce metallo-β-lactamases (MBLs) which break down antibiotics like carbapenems, leaving the drugs unable to treat infections.
Dr Alistair Farley (IOI) added: 'It’s a long journey involving teams of collaborators to go from strong enzyme inhibition in the lab to the development of a compound that is safe and effective in humans. This work shows the importance of understanding the precise mechanism of action of new inhibitors; and whilst promising, these inhibitors need to undergo considerable further optimisation and studies prior to being used clinically.'