Fig. 1: Discovery and biosynthesis of salivabactin.
a, In vitro anti-GAS activities of various SAL strains. The indicated SAL strains were placed in a well on an agar plate containing GAS lawn. The inhibitory activity was assessed by monitoring the presence or absence of inhibitory zone around SAL growth after 16 h incubation. b, Organization of the 16-gene operon encoding sar BGC. c, Comparison of LC–MS extracted ion chromatogram traces of the metabolic extracts from SAL and its mutant derivatives, showing the production of salivabactin associated with the sar BGC. EIC+ = 274.09 ± 0.01 (EIC, extracted-ion chromatogram) corresponds to salivabactin. d, Chemical structure of the two salivabactin isomers, salivabactin A and salivabactin B. e, Time-dependent killing assay. Incubation of exponential phase GAS growth with 10× MIC of salivabactin or penicillin G caused complete killing. Data graphed represent mean ± s.d. from three biological replicates. f, Mice (n = 15 per group) were given 107 CFUs of GAS intramuscularly, and antibiotics were given as a single i.m. dose at 1 h post infection. Kaplan–Meier survival curves with P values derived by the log-rank test are shown.
