Antibacterial Activity and Synergism of the Hybrid Antimicrobial Peptide, CAMA-syn

A 20-residue hybrid peptide CA(1-8)-MA(1-12) (CAMA) incorporating residues 1-8 of cecropin A (CA) and residues 1-12 of magainin 2 (MA) has high antimicrobial activity without toxicity. To investigate the effects of the total positive charges of CAMA on the antibacterial activity and toxicity, a hybrid peptide analogue (CAMA-syn) was designed with substitutions of $Ile^{10}\;and\;Ser^{16}$ with Lys. According to CD spectra, structure of CAMA-syn with increase of cationicity was very similar to that of CAMA in DPC micelle. CAMA-syn showed antimicrobial activity similar with CAMA while CAMA-syn has no hemolytic activity and much lower cytotoxicity against RAW 264.7 macrophage cells than CAMA. Also, CAMA and CAMA-syn significantly inhibited NO production by LPSstimulated RAW264.7 macrophage at 10.0∼20.0 $\mu$M. CAMA-syn displayed salt resistance on antimicrobial activity against Escherichia coli at the physiological concentrations of $CaCl_2\;and\;MgCl_2$. The combination studies of peptides and antibiotics showed that CAMA-syn has synergistic effects with synthetic compound and flavonoid against Enterococcus faecalis and VREF. CAMA-syn can be a good candidate for the development of new antibiotics with potent antibacterial and synergistic activity but without cytotoxicity.