The Mechanism of Action of Lysobactin
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- 作者：Wonsik Lee ; Kaitlin Schaefer ; Yuan Qiao ; Veerasak Srisuknimit ; Heinrich Steinmetz ; Rolf Müller ; Daniel Kahne ; Suzanne Walker
- 刊名：Journal of the American Chemical Society
- 出版年：2016
- 出版时间：January 13, 2016
- 年：2016
- 卷：138
- 期：1
- 页码：100-103
- 全文大小：365K
- ISSN：1520-5126
文摘
Lysobactin, also known as katanosin B, is a potent antibiotic with in vivo efficacy against Staphylococcus aureus and Streptococcus pneumoniae. It was previously shown to inhibit peptidoglycan (PG) biosynthesis, but its molecular mechanism of action has not been established. Using enzyme inhibition assays, we show that lysobactin forms 1:1 complexes with Lipid I, Lipid II, and Lipid IIAWTA, substrates in the PG and wall teichoic acid (WTA) biosynthetic pathways. Therefore, lysobactin, like ramoplanin and teixobactin, recognizes the reducing end of lipid-linked cell wall precursors. We show that despite its ability to bind precursors from different pathways, lysobactin’s cellular mechanism of killing is due exclusively to Lipid II binding, which causes septal defects and catastrophic cell envelope damage.