Fig. 4 | Nature Communications

Fig. 4

From: Discovery of cationic nonribosomal peptides as Gram-negative antibiotics through global genome mining

Fig. 4

Brevicidine and laterocidine show bactericidal activity, a low risk of resistance and efficacy in a mouse thigh infection model. a Time-kill assays. E. coli were grown to early phase and challenged with ten times the MIC of antibiotics. Data are representative of three independent experiments ± s.d. b Bacterial growth kinetics. Optical densities of E. coli cells exposed to two times the MIC of antibiotics. c CNRP treatment resulted in the lysis of E. coli. Figures b, c are representative of three independent experiments. d Resistance acquisition during serial passaging in the presence of sub-MIC levels of antimicrobials. e Atomic force microscopy of E. coli grown at 37 °C to mid-log phase (OD600 of ∼0.5) in the presence of ten times the MIC of CNRP antibiotics. Scale bar is 1 µm. The white square highlights the region scanned to obtain high-resolution topographical images of the brevicidine-treated cell surface. Scans are representative of two independent experiments. f Efficacy of brevicidine and laterocidine in a mouse thigh model infected by E. coli. Brevicidine (30 mg kg−1) or laterocidine (15 mg kg−1) treatment (twice) of E. coli thigh infections (five mice) leads to a reduced number of viable bacteria after 26 h. Significant differences between groups analyzed by the Mann–Whitney test (*P < 0.01). For a–f, con negative control, bre brevicidine, lat laterocidine, ply polymyxin, lev levofloxacin, chl chloramphenicol, and cfp ciprofloxacin

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