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 II(A)(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.
authors.affiliation: Department of Microbiology and Immunology, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Wonsik
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Harvard Medical School , Boston, Massachusetts 02115, United States.|Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Schaefer
authors.affiliation: Department of Microbiology and Immunology, Harvard Medical School , Boston, Massachusetts 02115, United States.|Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Veerasak
authors.initials: V
authors.lastname: Srisuknimit
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), and Pharmaceutical Biotechnology, Saarland University , Campus E8.1, 66123 Saarbrücken, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Steinmetz
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), and Pharmaceutical Biotechnology, Saarland University , Campus E8.1, 66123 Saarbrücken, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kahne
authors.affiliation: Department of Microbiology and Immunology, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
mesh_terms: D047630:Depsipeptides / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D013211:Staphylococcus aureus / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000378:metabolism*
chemical_list: D047630:Depsipeptides; C056790:katanosin B