Ruthenium-Based Aptamers to Combat Bacteria: A Scientific Breakthrough from Chimie ParisTech-PSL and the Institut Pasteur
After seven years of research, Professor Gilles Gasser and his team at the Institute of Chemistry for Life and Health Sciences – Chimie ParisTech-PSL, in collaboration with Dr. Marcel Hollentstein and Mélanie Hamon from the Institut Pasteur, have published a major breakthrough in the Journal of the American Chemical Society: the first selection of ruthenium-modified aptamers capable of selectively targeting and destroying the bacterium Streptococcus pneumoniae. This pioneering approach opens new perspectives in the fight against bacterial infections and antimicrobial resistance.
A Long-Term Collaboration to Tackle a Major Scientific Challenge.
In a recent article published in the prestigious Journal of American Chemical Society, the groups of Prof. Gilles Gasser at the Institute of Chemistry for Life and Health Sciences at Chimie ParisTech-PSL in collaboration with Dr. Marcel Hollentstein from Institut Pasteur could demonstrate, for the first time, that the modification of aptamers (i.e., short DNA strands capable of binding to targets) with Ruthenium polypyridyl complexes allows selectively targeting Gram-positive Streptococcus pneumoniae bacteria, a very problematic strain in medicine. Thanks to the presence of these ruthenium complexes that can act as photosensitizers for photodynamic therapy, light can be used to activate them and eradicate the bacteria.
An Innovative Approach to Design and Selection.
More precisely, this consortium of scientists could first prepare nucleotides equipped with various ruthenium complexes. They then demonstrated that some DNA polymerases could allow synthesising enzymatically oligonucleotides containing these Ruthenium complexes. Through a so-called SELEX experiment, one aptamer was found to have a high affinity (Kd value of 125 nM) for fixed Streptococcus pneumoniae bacteria.
Seven Years of Research Leading to a Promising Breakthrough.
Collectively, these results, obtained after 7 years of work of 2 PhD students and one post-doc, highlight the possibility of using nucleotides equipped with large modifications such as ruthenium polypyridyl complexes in SELEX to raise potent aptamers against entire bacterial targets. These findings open directions to convert aptamers into potent devices to combat antimicrobial resistance via PDT-based approaches.