Revolutionizing Antibiotic Discovery: An Ultra-Throughput Droplet Microfluidics and Multi-Omics Pipeline

Xiangpeng Li with Edward Kalkreuter, Kristina Håkansson, Robert Spencer, and Ryan Rodgers of Florida State University in the U.S. are developing an ultra–high-throughput antibiotic discovery pipeline. This platform integrates droplet microfluidics with multi-omic analyses to screen billions of soil-derived microbes for novel compounds effective against multidrug-resistant Klebsiella pneumoniae. The approach co-cultures microbes with fluorescent target strains in microdroplets to simultaneously assess antibacterial potency and eukaryotic toxicity. The team utilizes high-throughput microdroplet screening and the 21 Tesla FT-ICR mass spectrometer at the National High Magnetic Field Laboratory (NHMFL) located at Florida State University, for rapid chemical dereplication, accelerating the finding of new natural product scaffolds that evade existing resistance mechanisms.