Skip navigation
Please use this identifier to cite or link to this item:
Title: A dual-mechanism antibiotic kills Gram-negative bacteria and avoids drug resistance
Contributors: Martin, James K
Sheehan, Joseph P
Bratton, Benjamin P
Moore, Gabriel M
Mateus, André
Li, Sophia Hsin-Jung
Kim, Hahn
Rabinowitz, Joshua D
Typas, Athanasios
Savitski, Mikhail M
Wilson, Maxwell Z
Gitai, Zemer
Issue Date: 20-May-2020
Abstract: 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 that SCH-79797 has two independent cellular targets, folate metabolism and bacterial membrane integrity, and outperforms combination treatments in killing MRSA persisters. Building on the molecular core of SCH-79797, we developed a derivative, Irresistin-16, with increased potency and showed its efficacy against Neisseria gonorrheae in a mouse vaginal infection model. This promising antibiotic lead suggests that combining multiple MoAs onto a single chemical scaffold may be an underappreciated approach to targeting challenging bacterial pathogens.
Appears in Collections:Research Data Sets

Files in This Item:
File Description SizeFormat 
SCH_fluorescenceAndMetabolism_Data.tar.gz649.76 MBUnknownView/Download
README.txt1.18 kBTextView/Download

Items in Dataspace are protected by copyright, with all rights reserved, unless otherwise indicated.