Therapeutic Approach to Combat Antimicrobial Resistance
Fighting antimicrobial resistance with individualized antisense oligonucleotides and through a collaborative philosophy.
Antimicrobial resistance (ARS), e.g. antibiotic resistance, is one of the world’s most pressing global health problems. As of June 2022, almost 5 million deaths per year had been related to ARS, making it one of the top five global diseases, before HIV and Malaria. As a distinguishing feature, ARS equally threatens industrial as well as developing countries. Causes for ARS are of course the imprudent use of antibiotics in agriculture and human healthcare. But also the growing human population and the rapidly progressing climate change foster ARS propagation among microbes. Clearly, there is a dire need to search for new antibiotic substances, and importantly, to raise social awareness and self-responsibility in handling antimicrobial compounds.
A valuable approach will be to establish a high-throughput test-system for the development of antisense oligonucleotide (ASO) therapeutics. ASO’s are short nucleotide oligomers binding to complementary mRNA sequences, thereby modifying gene expression. The basis for the suggested approach is the high-throughput screening for (randomized) ASOs that effectively inhibit the growth of antibiotic-resistant strains. ASO’s will be transcribed from a plasmid, and flanked by specific ribonuclease-resistant RNA structures, protecting them from degradation. Selected ASO’s can then further be validated for treatment. Therefore, the selection of efficient vesicles for improved bacterial uptake will have a strong focus. Along with the experimental setup, data will be collected in a collaborative approach on a publicly available databank, providing starting points for the design of new antimicrobial therapeutic strategies. While ASO therapy for rare diseases, such as muscular atrophy (SMA), is extravagantly expensive, treating ARS infections will be a much broader field of application. This will significantly affect prizes of ASO-based treatments.
Image Credit: Falko Korn, courtesy of Sophie Korn
Sophie Korn, Lindau Alumna 2022
Goethe University, Germany