Integrated chemical and biological profiling for the discovery of antibiotics against resistant pathogens

Natural products, NPs, are prolific sources of therapeutics, particularly antibiotics. Numerous NP antibiotics were discovered from 1940-1960 however, the discovery rate declined as known compounds were repeatedly discovered. This led to a decrease in this research and contributed to the antimicrobial resistance, AMR, crisis. This project uses computational platforms to discover NP antibiotics to combat the AMR crisis without constant rediscovery. A profiling platform, ResistoMAP, screened a NP library and antimicrobial standards against a panel of 29 drug-resistant strains of Escherichia coli. A software, NP Analyst, combined these profiles with mass spectrometry, MS, to identify bioactive metabolites. Focusing on unique MS and ResistoMAP profiles, three candidates were selected for characterization. Two were identified as streptorubin B and undecylprodigiosin, while the third demonstrates activity and is being studied further. This suggests that the technique outlined throughout this project is effective in identifying compounds effective against resistant pathogens while minimizing rediscovery.