Bacteria are increasingly becoming resistant to antibiotics, posing a significant threat to modern medicine and global public health. Therefore, it is crucial to find new forms of antibiotics. Wim Velema and his team are working on a new type of antibiotic. With the support of NWO financing, Velema will conduct pre-clinical studies within his project 'Next-generation Antisense Antibiotics' to investigate the efficacy of this new antibiotic.
Antisense therapy
In the 1990s, 'Antisense therapy' was developed. This method allows the function of certain genes in a cell to be blocked. By introducing an oligonucleotide (ASO) into the cell, it binds to a target gene. This binding can prevent the target gene from functioning normally, potentially causing the cell to die. This method can be used to neutralise bacteria, making it a potential antibiotic.
"Unfortunately, Antisense therapy has never become very successful, mainly because the delivery of ASOs into the cell proved to be very challenging," explains Wim Velema. "Therefore, our team has developed a new method to deliver ASOs to the right place in bacteria, using specialised molecules called siderophores."
Siderophores
Siderophores are secreted by bacteria. Outside the cell, they bind to iron. When siderophores are bound to iron, bacteria reabsorb them. Velema states, "The beauty of it is that bacteria always take up siderophores when they are bound to iron, even if we attach other molecules as cargo to the siderophores. This way, we can smuggle an ASO into a cell. In our lab, we have attached a synthetic siderophore to an ASO and thus rendered the E. coli bacteria harmless."
From research to application
In the next two years, Velema and his team will study their promising invention in vivo. Additionally, they are already exploring the scale-up of siderophore-ASO production and the commercialisation of the technique. Velema says, "There is still a long way to go, but it would be fantastic if we succeed in bringing our idea to clinical application."
About the NACTAR programme by NWO
The NACTAR programme by NWO focuses on researching new sources and alternatives for antibiotics. In this round, a total of almost 1.6 million euros has been made available in collaboration with the Ministry of Health, Welfare, and Sport. The research budget enables studies to be conducted, validating the effectiveness of new antimicrobial substances and methods. This can make a significant contribution to the treatment of diseases caused by bacteria that current medicines and antibiotics no longer combat.