Figure 3 |. Teixobactin binds to cell wall precursors.

a, Impact of teixobactin (TEIX) on macromolecular biosyntheses in S. aureus. Incorporation of ³H-thymidine (DNA), ³H-uridine (RNA), ³H-leucine (protein), and ³H-glucosamine (peptidoglycan) was determined in cells treated with teixobactin at 1 × MIC (grey bars). Ciprofloxacin (8 × MIC), rifampicin (4 × MIC), vancomycin (2 × MIC) and erythromycin (2 × MIC) were used as controls (white bars). Data are means of 4 independent experiments ± s.d. b, Intracellular accumulation of the cell wall precursor UDP-MurNAc-pentapeptide after treatment of S. aureus with teixobactin. Untreated and vancomycin (VAN)-treated (10 × MIC) cells were used as controls. UDP-MurNAc-pentapeptide was identified by mass spectrometry as indicated by the peak at m/z 1,149.675. The experiment is representative of 3 independent experiments. c, The effect of teixobactin on precursor consuming reactions. Experiments were performed in 3 biological replicates and data are presented as mean ± s.d. d, Complex formation of teixobactin with purified cell wall precursors. Binding of teixobactin is indicated by a reduction of the amount of lipid intermediates (visible on the thin-layer chromatogram). The figure is representative of two independent experiments. e, A model of teixobactin targeting and resistance. The teixobactin producer is a Gram-negative bacterium protected from this compound by exporting it across the outer membrane permeability barrier (upper panel). In target Gram-positive organisms lacking an outer membrane, the targets are readily accessible on the outside where teixobactin binds precursors of peptidoglycan (PG) and WTA. CM, cytoplasmic membrane; CW, cell wall; OM, outer membrane; T, teixobactin.