An enhancer peptide for membrane-disrupting antimicrobial peptides.
BACKGROUND
NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4) by substitution of all acidic amino acid residues with amides (i.e., Glu --> Gln, and Asp --> Asn).


RESULTS
In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-alpha, polymyxin B, and nisin) killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-alpha against Staphylococcus aureus), whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at <or= 300 microg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin) were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-alpha permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P.


CONCLUSIONS
NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane.
Ueno
Satoshi
S
Division of Insect Sciences, National Institute of Agrobiological Sciences, Oowashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
Kusaka
Kohtaro
K
Tamada
Yasushi
Y
Zhang
Hong
H
Minaba
Masaomi
M
Kato
Yusuke
Y
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; C550004:NP4P peptide; D010455:Peptides