Development of long lasting antibiotics

Project supported by CARe, 773 SEK

Participants: Carl-Johan Wallentin, Morten Grøtli, Per Sunnerhagen, Anne Farewell and Jonas Warringer

Constant emergence of new mutations in large bacterial populations and Darwinian selection for the most resistant of these by drug use means that drug resistance is unavoidable. However, the speed of drug resistance development depends on the number and strength of drug resistant mutations. We conjectured that drug resistance can be drastically reduced by developing and using antibiotics with intrinsically slow drug resistance development. By incorporating the key mechanism responsible for antibiotic resistance as a structural refinement element in the drug development we believe it possible to extend drug longevity and reduce risks of therapy failure. Molecular starting points include complex natural products that have showcased potent activities against both gram-positive and gram-negative strains of clinical relevance. The project targets to develop these natural products to a collection of pre-clinical dual action lead compounds resilient to drug resistance development. These characteristics are key to the next generation antibiotics that will safeguard against a future situation similar to the present.
The integrative platform that will guide this initiative provide the means for a continuous development of novel antimicrobials together with the tools necessary of gaining an extended insight into the mechanism of resistance development.