Tissue-Based Target Profiling to De-Risk Drug Discovery for Multi-Drug Resistant Klebsiella

Joan Mecsas in collaboration with Bree Aldridge and Ralph Isberg all from Tufts University in the U.S. will develop portable tissue-specific in vivo and in vitro models that will be standardizable to accelerate Gram-negative drug discovery. In parallel, they will create a genetic target screening technology to identify drug-susceptible genes and pathways across a diverse set of multidrug-resistant Klebsiella pneumoniae strains in tissue-specific models. Their approach seeks to mitigate two key challenges to drug discovery: the high degree of bacterial genetic heterogeneity among multidrug-resistant Klebsiella, and the multiple distinct tissue environments inhabited by Klebsiella, both of which can significantly impact drug responses.  The overarching goals are to generate a compendium of pan-targets and dual-pan-targets, which include critical contextual information about conditionality on tissue niche and strain, and to de-risk drug discovery by using tractable tissue-based models for discovery, prioritization, and evaluation of new therapeutics.

This grant is funded by The Novo Nordisk Foundation.