Figure 1.

Peptides L6 and L8 are active in vitro against Gram-negative clinical isolates and interact with LPS but have limited activity in vivo. In vitro MIC values of peptides or vancomycin alone and MIC values of peptides combined with vancomycin or vancomycin in combination with peptides against Gram-negative bacteria were determined via checkerboard assays either in medium containing no LPS (A) or in medium containing smooth (Sm) LPS, rough (Ra) LPS or deep rough (Rd) LPS (B). The FIC values were defined as the ratio of either the MIC value of the peptide in combination with vancomycin over the MIC value of the peptide alone (FIC_L6 and FIC_L8) or the ratio of the MIC value of vancomycin combined with peptide over the MIC value of vancomycin alone (FIC_Vancomycin). The degree of α-helicity of L6 and L8 either in medium containing no LPS, Sm-LPS, Ra-LPS or Rd-LPS was determined with CD spectroscopy. Relative helicity was calculated using circular dichroism analysis using neural networks (CDNN) software (C). Zebrafish larvae survival rates after infection with A. baumannii 1757 and treatment with peptides, vancomycin or combinations of peptide and vancomycin via caudal vein injection (D). The data are presented as mean ± standard deviation from three independent experiments.