Identification of Compounds with Novel Mechanisms of Action Targeting Klebsiella pneumoniae

Daniel Inaoka of the Institute of Tropical Medicine Nagasaki University and Yohei Doi of Fujita Health University, both in Japan, will aim to identify novel antibacterial compounds with new mechanisms of action (MoAs) against Klebsiella pneumoniae. By integrating high-throughput screening, transcriptomic profiling (Quartz-seq2), and genomic analysis, they will systematically discover and characterize compounds with distinct MoAs from existing antibiotics. Approximately 260,000 compounds from Japan’s two largest academic libraries will be screened. Active hits will be confirmed and validated, with transcriptomic clustering and machine learning applied to efficiently identify candidates with new MoAs. Resistant mutants will then be generated and analyzed by whole-genome sequencing to elucidate molecular targets.

This grant is funded by The Wellcome Trust.