The Gram-negative Antibiotic Discovery Innovator (Gr-ADI) is a joint initiative by Novo Nordisk Foundation, the Gates Foundation and Wellcome Trust, see https://gcgh.grandchallenges.org/challenge/innovations-gram-negative-antibiotic-discovery.

The project aims to tackle the emerging health crisis due to antibiotic resistance in Klebsiella pneumoniae. Our team of C4D partners will apply innovative concepts and beyond-state-of-the-art technologies to unlock untapped chemical diversity from natural ecosystems. For this we will use a combination of culture-independent compound sourcing, ecology-inspired elicitation approaches and high-throughput microfluidics. By mining microbiomes from marine, plant, and human-associated environments, we will identify novel biosynthetic pathways and natural products with potent anti-Klebsiella activity. Compounds will be prioritized based on chemical novelty, spectrum of bioactivity, level of expression and initial pharmaceutical evaluation. The most promising compounds will undergo structural elucidation and detailed profiling against multidrug-resistant Klebsiella strains. Our approach is designed to reveal not only new molecules, but also novel mechanisms of action and ecological triggers for antibiotic production. Through this ambitious, interdisciplinary effort, we aim to deliver new antibiotic scaffolds and discovery strategies.

• actinomycetes
• antibiotics
• drug resistance
• microbial ecology
• synthetic biology

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