What is it about?
Some resistant bacteria produce metallo-beta-lactamases, zinc-dependent enzymes that destroy carbapenems such as meropenem, leaving very few treatment options. Molecules that capture zinc (chelators) can disable these enzymes. We synthesized a series of polypyridine compounds able to bind zinc and tested whether they could restore the activity of meropenem against three resistant bacteria isolated from patients with bloodstream infections: Klebsiella pneumoniae, Enterobacter cloacae and Stenotrophomonas maltophilia, all producing metallo-beta-lactamases. We also attached a short peptide to one compound to help it enter bacteria. Four of the compounds acted synergistically with meropenem against all tested strains, restoring its effect, while one worked only against NDM- and VIM-producing bacteria.
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Photo by Hans Reniers on Unsplash
Why is it important?
Metallo-beta-lactamase-producing bacteria are among the most threatening resistant pathogens, and inhibitors of these enzymes are urgently needed. This study identifies polypyridine ligands as promising candidates to be combined with carbapenems, providing a chemical basis for the development of new adjuvant therapies.
Perspectives
This was the starting point of a fruitful collaboration with chemists in Catania on metallo-beta-lactamase inhibitors. As a clinician, I find it rewarding to bring strains from our patients into the chemistry laboratory, hoping that one day the molecules developed there will come back to the bedside.
Professor Stefano Di Bella
Universita degli Studi di Trieste
Read the Original
This page is a summary of: Polypyridine ligands as potential metallo-β-lactamase inhibitors, Journal of Inorganic Biochemistry, February 2021, Elsevier,
DOI: 10.1016/j.jinorgbio.2020.111315.
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