In a collaboration between the Central Laser Facility's (CLF) Octopus Imaging Cluster and the University of Sheffield and Imperial Collage London, scientists have developed a new compound that has the ability to kill both gram-positive and gram-negative antibiotic resistant bacteria. This research could pave the way towards vital new treatments for antibiotic resistant superbugs.
Antimicrobial resistant strains are responsible for 25,000 deaths in the EU each year and this growing threat will only worsen if we are unable to develop new treatments. The compound, which is a ruthenium(II) complex developed within the group of Prof Jim Thomas at the University of Sheffield. Is effective against both gram-positive and gram-negative bacteria, including therapeutically resistant pathogens like MRSA.
With the help of the super-resolution nanoscopy facilities at the Octopus Laser Facility, which is part of the CLF, the mechanism of action of the new compound was identified. Using the intrinsic luminescence of the compound it was found that it passes through the cell wall of both gram-positive and gram-bacteria to bind with DNA. These studies were carried out in collaboration with Dr Jorge Bernardino de la Serna (Imperial College London), a spectroscopist at the CLF at the time and a continuing visiting scientist of the CLF.
Although previous research by the group, which also included studies at Octopus, had discovered a compound that targets gram-negative bacteria, this latest lead has great potential has a broad-spectrum antimicrobial, and whilst this research is still in its early stages, it shows promise as a potential future treatment for antibiotic resistant infections caused by a wide range of bacteria including pathogenic E.coli and MRSA.
The University of Sheffield's Professor of Bio-inorganic Chemistry Jim Thomas said: "The identification of these novel antimicrobials and their mode of action has been greatly accelerated by the intrinsic luminescent properties. To be able to probe their uptake, intracellular localization, and directly see how they kill bacteria at the amazing resolutions supplied by STED has been a huge catalyst in their development."
Dr Jorge Bernardino de la Serna from Imperial College London said:
“The ruthenium-based dyes developed by Professor Thomas uniquely display fluorescence properties which can nicely resolved employing a type of super resolution microscopy, STED (Stimulation Emission Depletion). The cellular laboratories at CLF, equipment capabilities and know-how of the experienced staff within Octopus has been instrumental to be able to resolve the mechanism of action of this antimicrobials at the nanoscale".
Read the paper here: https://pubs.rsc.org/en/content/articlehtml/2020/sc/d0sc03410j