UK Scientists Develop New Compound Which Kills Both Types of Antibiotic-resistant Bacteria

Priscilla Lynch 

September 11, 2020

UK researchers have developed a new compound that is able to kill both gram-positive and gram-negative antibiotic-resistant bacteria.

While gram-positive and gram-negative bacteria have different cell wall structures, the new antibiotic compound is able to pass through the cell wall of both forms of bacteria and then bind to the DNA.

The findings, published in  Chemical Science,  pave the way for developing new treatments for all kinds of antibiotic resistant bacteria, including the gram-positive MRSA and gram-negative E.coli.

The research team from the University of Sheffield has previously developed new compound leads that specifically target gram-negative bacteria, but this new compound is a broad spectrum antimicrobial. In this study six luminescent, mononuclear ruthenium(II) complexes based on the tetrapyridophenazine (tpphz) and dipyridophenazine (dppz) ligands are reported.

The therapeutic activities of the complexes against gram negative bacteria (E.coliA.baumanniiP.aeruginosa) and gram-positive bacteria (E.faecalis and S.aureus) including pathogenic multi- and pan-drug resistant strains were assessed.

Estimated minimum inhibitory and bactericidal concentrations show the activity of the lead compound is comparable to ampicillin and oxacillin in therapeutically sensitive strains and this activity was retained in resistant strains.

Unlike related dinuclear analogues, the lead compound does not damage bacterial membranes but is still rapidly taken up by both gram-positive and gram-negative bacteria in a glucose independent manner.

Prof Jim Thomas, Principal Investigator of the research from the University of Sheffield, said: “Antimicrobial resistance is an increasing problem with many studies predicting a medical global emergency, so broad spectrum antimicrobials which work against resistant pathogens are urgently needed."

“As the compound is luminescent it glows when exposed to light. This means we were able to follow the uptake and effect on bacteria using advanced microscopy techniques…”

Smitten KL, Thick EJ, Southam HM, de la Serna JB, Foster SJ, Thomas JA. Mononuclear ruthenium(II) theranostic complexes that function as broad-spectrum antimicrobials in therapeutically resistant pathogens through interaction with DNA†. Chem Sci, 2020, 11, 8828. doi: 10.1039/d0sc03410j. Abstract

This article originally appeared on Univadis, part of the Medscape Professional Network.

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