A dual-mechanism antibiotic kills Gram-negative bacteria and avoids drug resistance

James K. Martin, Joseph P. Sheehan, Benjamin Bratton, Gabriel M. Moore, André Mateus, Sophia Hsin-Jung Li, Hahn Kim, Joshua D. Rabinowitz, Athanasios Typas, Mikhail M. Savitski, Maxwell Z. Wilson & Zemer Gitai
The rise of antibiotic resistance and declining discovery of new antibiotics have created a global health crisis. Of particular concern, no new antibiotic classes have been approved for treating Gram-negative pathogens in decades. Here, we characterize a compound, SCH-79797, that kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism of action (MoA) with undetectably-low resistance frequencies. To characterize its MoA, we combined quantitative imaging, proteomic, genetic, metabolomic, and cell-based assays. This pipeline demonstrates...

Registration Year

  • 2020
    26

Resource Types

  • Dataset
    26

Affiliations

  • Princeton University
    15
  • Boston University
    1