Extended Data Figure 6: Time course of incorporation of tritium-labelled metabolic precursors into lugdunin-treated B. subtilis.
From: Human commensals producing a novel antibiotic impair pathogen colonization
B. subtilis 168 (trpC2) is a widely used model organism for mode of action investigations and was also used for orienting studies on the mechanism of lugdunin. Susceptibility of B. subtilis and S. aureus to lugdunin is similar (Table 1), with an MIC for B. subtilis of 4 μg ml−1 in the Belitzky minimal medium used in this assay. a–d, Incorporation of thymidine into DNA (a), uridine into RNA (b), leucine into protein (c) or N-acetylglucosamine into peptidoglycan (d) ceased within minutes during lugdunin treatment. The experiment was repeated on three days with three independent bacterial cultures. One representative experiment is shown. At a concentration of half the MIC (1/2 MIC), incorporation of precursors into all pathways ceased reproducibly. At 1/8 MIC, incorporation continued repeatedly in parallel with the untreated control. At 1/4 MIC, the depicted experiment shows protein and peptidoglycan syntheses slightly more impaired than DNA and RNA syntheses, whereas the opposite occurred in another experiment. In summary, all four metabolic pathways seem to be equally impaired by lugdunin.
