美国普林斯顿大学Zemer Gitai研究组发现一种新型抗生素，可杀死革兰氏阴性菌并不会产生耐药。相关论文2020年6月3日在线发表于《细胞》。

Title: A Dual-Mechanism Antibiotic Kills Gram-Negative Bacteria and Avoids Drug Resistance

Author: James K. Martin, Joseph P. Sheehan, Benjamin P. 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

Issue&Volume: 2020-06-03

Abstract: The rise of antibiotic resistance and declining discovery of new antibiotics has createda global health crisis. Of particular concern, no new antibiotic classes have beenapproved for treating Gram-negative pathogens in decades. Here, we characterize acompound, SCH-79797, that kills both Gram-negative and Gram-positive bacteria througha unique dual-targeting mechanism of action (MoA) with undetectably low resistancefrequencies. To characterize its MoA, we combined quantitative imaging, proteomic,genetic, metabolomic, and cell-based assays. This pipeline demonstrates that SCH-79797has two independent cellular targets, folate metabolism and bacterial membrane integrity,and outperforms combination treatments in killing methicillin-resistant Staphylococcus aureus (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 gonorrhoeae in a mouse vaginal infection model. This promising antibiotic lead suggests thatcombining multiple MoAs onto a single chemical scaffold may be an underappreciatedapproach to targeting challenging bacterial pathogens.

DOI: 10.1016/j.cell.2020.05.005

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30567-5