The Mechanism of Action of Lysobactin

Wonsik Lee; Kaitlin Schaefer; Yuan Qiao; Veerasak Srisuknimit; Heinrich Steinmetz; Rolf Müller; Daniel Kahne; Suzanne Walker

doi:10.1021/jacs.5b11807

The Mechanism of Action of Lysobactin

Wonsik Lee, Kaitlin Schaefer, Yuan Qiao, Veerasak Srisuknimit, Heinrich Steinmetz, Rolf Müller, Daniel Kahne, Suzanne Walker

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

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 IIA_WTA, 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.

Original language	English
Pages (from-to)	100-103
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	138
Issue number	1
DOIs	https://doi.org/10.1021/jacs.5b11807
State	Published - 13 Jan 2016
Externally published	Yes

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title = "The Mechanism of Action of Lysobactin",

abstract = "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.",

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T1 - The Mechanism of Action of Lysobactin

AU - Lee, Wonsik

AU - Schaefer, Kaitlin

AU - Qiao, Yuan

AU - Srisuknimit, Veerasak

AU - Steinmetz, Heinrich

AU - Müller, Rolf

AU - Kahne, Daniel

AU - Walker, Suzanne

PY - 2016/1/13

Y1 - 2016/1/13

N2 - 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.

AB - 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.

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The Mechanism of Action of Lysobactin

Abstract

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