The range of antibiotics available to combat bacterial infectious diseases is diminishing due to the development of resistance to all classes of antibiotics.
The emergence of Carbapenem-resistant Enterobacteriaceae (CRE) is one of the most significant and urgent threats to global human health. CRE strains that have acquired and expressed genes encoding for extended-spectrum β-lactamases with carbapenemase activity have now been reported across the globe.
One strategy for prolonging the use of existing antibiotics has been to develop adjuvants that inhibit the function of β-lactamases and thus restore the bacteria’s sensitivity to the β-lactam antibiotic (e.g. clavulanic acid and tazobactam). However, for carbapenemase enzymes which are class B β-lactamases (i.e. the metallo-β-lactamases (MBLs)), such inhibition strategies have, so far, been ineffective.
Consequently, there is a market need for effective inhibitors of class B MBLs as adjuvants for carbapenems. These MBL inhibitors have the potential to prolong the use of carbapenem antibiotics and address the urgent threat of CRE.
Researchers from the University of Queensland have identified a mechanism by which class B MBLs can be inactivated and have translated this knowledge to develop inhibitors of these enzymes. These inhibitors have the potential to be used as an adjuvant with carbapenem antibiotics to restore the activity of carbapenems and treat infections caused by CRE.