What is it about?
Some of the most dangerous resistant bacteria produce metallo-beta-lactamases (MBLs), enzymes such as NDM-1, VIM-1 and IMP-1 that destroy carbapenems, our last-resort antibiotics. These enzymes need zinc ions to work, so molecules that capture zinc (chelators) could switch them off and restore antibiotic activity. We tested four polypyridine compounds in the laboratory against three MBLs. Most of them blocked NDM-1 and VIM-1 very effectively, at very low concentrations: Bispicen was the best against VIM-1 and Trispicen against NDM-1. IMP-1, instead, was not inhibited. Computer docking studies showed that the compounds bind the enzyme active site and grab both zinc ions.
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Photo by Vedrana Filipović on Unsplash
Why is it important?
There are very few drugs active against MBL-producing bacteria, and no approved MBL inhibitor is widely available. These results identify polypyridine ligands as promising starting points for developing inhibitors that, combined with carbapenems, could restore their effectiveness against some of the most threatening resistant pathogens.
Perspectives
As a clinician, I am always fascinated by basic chemistry that may one day reach the bedside. This collaboration with chemists in Catania and microbiologists in L Aquila tackles one of the hardest problems in antimicrobial resistance: metallo-beta-lactamases. Inhibiting the enzyme rather than inventing new antibiotics is a smart strategy.
Professor Stefano Di Bella
Universita degli Studi di Trieste
Read the Original
This page is a summary of: The in vitro inhibitory activity of polypyridine ligands towards subclass B1 metallo-β-lactamases, Results in Chemistry, January 2023, Elsevier,
DOI: 10.1016/j.rechem.2023.100986.
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