Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics

• DOI: 10.1038/s41467-017-02470-8
• Publication Date: 2017-12-27T12:33:43Z
• Authors: David C. Earl; P. Brent Ferrell; Nalin Leelatian; Jordan T. Froese; Benjamin J. Reisman; Jonathan M. Irish; Brian O. Bachmann
• Keywords: Metabolome

Discovering bioactive metabolites within a metabolome is challenging because there generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles primary human tissue comprise platform used to discover novel microbial with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling. Arrayed are tested against acute myeloid leukemia patient bone marrow molecules that specifically targeted blast cells nonleukemic immune subsets the same biopsy revealed. Cell-targeting polyketides identified extracts from biosynthetically prolific bacteria, previously unreported blast-targeting anthracycline polyene macrolactam alternates between blasts nonmalignant by way light-triggered photochemical isomerization. High-resolution profiling mass cytometry confirms mechanisms validate initial observations.