P18 (KWKLFKKIPKFLHLAKKF-NH(2)) is an alpha-helical
antimicrobial peptide designed from a
cecropin A-
magainin 2 hybrid. In this study, P18 was found to show strong antimicrobial activity against several
antibiotic-resistant bacterial and fungal strains. Both the
salt resistance on antimicrobial activity and the synergistic effect with clinically used
antibiotic agents are critical factors in developing effective
peptide antibiotic drugs. For this reason, we investigated the
salt resistance of P18 to antagonism by NaCl, CaCl(2), and MgCl(2) on antimicrobial activity and the synergistic effect of P18 with
vancomycin against
vancomycin-resistant Enterococcus faecium (VREF). Compared to
magainin 2, P18 showed strong resistance on antimicrobial activity against bacterial strains and C. albicans under high NaCl concentrations of 100-200 mM. In addition, P18 displayed much greater
salt resistance on antibacterial activity against Gram-negative bacteria at the physiological or elevated concentrations of CaCl(2) and MgCl(2) than
magainin 2. Furthermore, the combination study revealed that P18 has a relatively effective synergistic effect with
vancomycin against VREF. Thus, these results support that P18 may prove to be a
salt-resistant
antibiotic peptide potentially useful in the treatment of
cystic fibrosis patients as well as a valuable adjuvant for antimicrobial
chemotherapy.