Salt resistance and synergistic effect with vancomycin of alpha-helical antimicrobial peptide P18.
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.
Shin
Song Yub
SY
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, Korea.
Yang
Sung-Tae
ST
Park
Eun Ju
EJ
Eom
Soo Hyun
SH
Song
Woo Keun
WK
Kim
Yangmee
Y
Hahm
Kyung-Soo
KS
Kim
Jae Il
JI
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002176:Candida albicans / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000378:metabolism; D054806:Magainins; D015636:Magnesium Chloride / Q000494:pharmacology; D010452:Peptide Biosynthesis; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012492:Salts / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology*; D029867:Xenopus Proteins
D000277:Adjuvants, Pharmaceutic; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D054806:Magainins; C447608:P18 antimicrobial peptide; D010455:Peptides; D012492:Salts; D029867:Xenopus Proteins; D015636:Magnesium Chloride; C053301:magainin 2 peptide, Xenopus; D012965:Sodium Chloride; D014640:Vancomycin; D002122:Calcium Chloride