Antimicrobial resistance (AMR) is increasingly being recognised as one of the biggest global health concerns. The inability to treat bacterial infections could lead to an annual death toll of 10 million worldwide by 2050 and make many of the medical advances of the 20th century obsolete. The 3-decade void in antibiotic drug discovery means that recently discovered therapeutic targets have not been fully exploited in this field. An example of a therapeutic target that has so far been under exploited in AMR are the G-quadruplexes, which have been extensively studied in cancer. G-quadruplexes are quadruply-stranded helical structures found in guanine-rich oligonucleotides and are thought to play essential biological roles including regulation of gene expression. Here we describe preliminary investigations aimed at exploring the role that G-quadruplexes may play in regulating the expression of genes responsible for antibiotic resistance in Pseudomonas aeruginosa. The latter is responsible for many life-threatening infections and has been identified as one of three highest priority pathogens in a recent World Health Organisation report. The talk will focus on the biophysical characterisation of a series of quadruplex-forming sequences. We will show that some of them form robust G-qudruplexes and they may be potential targets for the development of new small-molecule drugs.
Ramón Vilar is Professor of Medicinal Inorganic Chemistry and is currently Director of Research in the Department of Chemistry. His research focuses on the synthesis and biomedical applications of metal complexes and supramolecular assemblies. In particular, his group is interested in understanding the interactions of metal complexes with DNA and proteins, and in the development of novel molecular probes for sensing and bio-imaging.