a Therapeutic effect of (R)- and (S)-ZG197 against USA300 infection in zebrafish. Zebrafish (n = 11 animals) were infected with 7 × 106 CFU of USA300, and compounds were administered at a single dose of 50 mg/kg. DMSO (5%) and vancomycin were administered as controls. Therapeutic effect of (R)-ZG197 against lethal infection by Newman (b) and the ΔclpP mutant (c). Zebrafish (n = 11 animals) were infected with 7 × 107 CFU of Newman (b) or 3 × 107 CFU of the ΔclpP mutant (c), and compounds were administered to infected zebrafish at 50 mg/kg. Vancomycin and ONC212 were used as controls. d Therapeutic effect of (R)-ZG197 on the clinical MRSA isolates infected zebrafish. Zebrafish (n = 11 animals) were infected with 5 × 107 CFU of XJ049, and compounds were administered at a single dose of 50 mg/kg. DMSO (5%), antibiotics (vancomycin, erythromycin, and oxacillin), and the global activator ONC212 were used as controls. e Quantitation of necrotic skin lesion size of initial (left panel) and 4 days post-infection (right panel). Vancomycin was used as a positive control. Data are shown as mean ± SD (n = 9 animals). f Representative images showing necrotic skin lesions 4 days post-infection. The scale bar represents 1 cm. g Effects of our activators on bacterial counts in the skin samples (n = 8 biologically independent samples). Skin tissue was excised from mice infected with USA300 4 days post-infection and plated onto TSA to enumerate CFUs. h Micrographs of H&E-stained skin tissues after the indicated treatments. The scale bar represents 1 mm (Top) and 0.1 mm (Bottom). Statistical differences were analyzed using Log-rank tests (a–d) and two-tailed unpaired Student’s t-tests (e, g). Exact P values are provided. ns, no significance. Data (e, g) are presented as mean ± SD (error bars). Source data are provided as a Source Data file.
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