a, b, Human erythrocytes were treated for 1 h (a) and rat primary hepatocytes were treated for 24 h (b) with analogues 2 and 9. c, MRSA MW2 persisters were treated with analogue 9. The data points on the x axis are below the level of detection (2 × 102 CFU ml−1). a–c, Individual data points (n = 3 biologically independent samples) and mean ± s.d. are shown. d, Representative configurations of molecular dynamics simulations of analogue 2 interacting with lipid bilayers (108 phosphatidylglycerol lipids, 72 Lys-PG lipids and 10 DPG lipids; see Supplementary Methods for atomic rendering). Simulations were repeated five times with similar results. e, Free energy profiles of analogue 2, CD437 and adarotene penetrating the membrane as a function of the distance between the COM of the retinoids and the lipid bilayer. The dot-dashed line marks the membrane surface, averaged from the COM location of phosphate groups in outer leaflet. Individual data points (n = 3 independent simulations) and mean ± s.d. are shown. f, The plasma concentrations of analogue 2 after a single injection of analogue 2 (20 mg kg−1, i.p., 3 mice per time point) were measured using LC–MS/MS. Pharmacokinetic analysis was conducted using Phoenix WinNonlin software version 6.3. Individual data points (n = 3 biologically independent animals) and mean ± s.d. are shown. The determined pharmacokinetic parameters are T max (the time taken to reach the maximum concentration) 0.5 h, C max (maximum concentration observed) 16.14 μg ml−1, AUC last (area under the curve to last time point) 16.38 h·μg ml−1, AUC inf (area under the curve to infinite) 16.54 h·μg ml−1, t 1/2 (half-life) 4.49 h, clearance 20.16 ml min−1 kg−1. g, Six mice per group (n = 6 biologically independent animals) were treated with control (5% Kolliphor + 5% ethanol, i.p.), vancomycin (25 mg kg−1, i.p.) or analogue 2 (10–80 mg kg−1, i.p.) every 12 h for 3 days. At 12 h after the last treatment, alanine aminotransferase (ALT) and blood urea nitrogen (BUN) were analysed. The concentrations of ALT (in international units per litre, IU l−1) and BUN (mg dl−1) in each mouse serum sample analysed are plotted as individual points and the mean ± s.d. is shown. Control and antibiotic treatments were analysed by one-way ANOVA and post hoc Tukey test, which demonstrated a lack of significant differences (P > 0.7 for all ALT and BUN samples). Source data