Metallo-beta-Lactamases, and Metallo-beta-Lactamase Inhibitors: updates

What is it about?

This REVIEW highlights the emergence and escalation of MBLs in Gram-negative bacteria. The relationships between different class B Beta-lactamases identified up to 2017 are represented by a phylogenetic tree. In addition, approved and/or clinical-phase serine beta-lactamase inhibitors are recapitulated to reflect the successful advances made in developing class A beta-lactamase inhibitors. Reported MBL Inhibitors, their inhibitory properties, and their purported modes of inhibition are delineated. Insights into structural variations of MBLs and the challenges involved in developing potent MBL inhibitors are also elucidated and discussed in this review.

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Why is it important?

The worldwide proliferation of life-threatening Metallo-Beta-lactamase (MBL)- producing Gram-negative bacteria is a serious concern for public health. MBLs are compromising the therapeutic efficacies of Beta-lactams, particularly carbapenems, which are last-resort antibiotics indicated for various multidrug-resistant bacterial infections. Inhibition of enzymes mediating antibiotic resistance in bacteria is one of the major promising means for overcoming bacterial resistance. Compounds having potential MBL-inhibitory activity have been reported, but none are currently under clinical trials. The need for developing safe and efficient MBL inhibitors (MBLIs) is obvious, particularly with the continuous spread of MBLs worldwide.

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