Liselot DEWACHTER

KU Leuven

Prize Award 2025

Exploiting CRISPR-Cas genome editing for smarter antibiotic target selection and drug design

Work summary

Due to the relentless increase in antibiotic-resistant bacterial infections, treatment failure is becoming more and more common, leading to an alarming amount of resistance-associated deaths. To turn the tide, new antibiotics are urgently needed. With pharmaceutical companies hesitant to develop new antibiotics due to low profitability and rapid resistance development, we have created an innovative strategy that can focus our efforts onto the most promising drug targets and lead compounds. By exploiting high-throughput CRISPR-Cas genome editing, we have introduced > 17.000 mutations in the E. coli genome to probe the functional requirements and mutational flexibility of three potential drug targets (FabZ, LpxC, MurA). Using our approach, we were able to accurately determine which targets and lead compounds are least amenable to resistance development and thereby prioritize them for drug development. Based on this solid proof of concept, we hope that our approach can help boost antibiotic development in the near future.

This research has been executed at the Center for Microbiology at VIB/KU Leuven. The research has also benefited from collaborations with the academic research groups of Prof. Wim Versées (VIB/VUB) and Prof. Wim Vranken (VUB), and our industrial partner Inscripta, Inc with whom we connected thanks to the VIB Technology Watch initiative.