Extended Data Figure 7: Model for the mechanism of action of teixobactin. | Nature

Extended Data Figure 7: Model for the mechanism of action of teixobactin.

From: A new antibiotic kills pathogens without detectable resistance

Extended Data Figure 7

Inhibition of cell wall synthesis by teixobactin. Lipid II, precursor of peptidoglycan, is synthesized in the cytoplasm and flipped to the surface of the inner membrane by MurJ48 or FtsW49. Lipid III, a precursor of wall teichoic acid (WTA), is similarly formed inside the cell and WTA lipid-bound precursors are translocated across the cytoplasmic membrane by the ABC-transporter TarGH50. Teixobactin (TEIX) forms a stoichiometric complex with cell wall precursors, lipid II and lipid III. Abduction of these building blocks simultaneously interrupts peptidoglycan (right), WTA (left) biosynthesis as well as precursor recycling. Binding to multiple targets within the cell wall pathways obstructs the formation of a functional cell envelope. Left panel, teixobactin targeting and resistance. The producer of teixobactin is a Gram-negative bacterium which is protected from this compound by exporting it outside of its outer membrane permeability barrier. The target Gram-positive organisms do not have an outer membrane. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; LTA, lipoteichoic acid; WTA, wall teichoic acid.

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