Effects of the terminal charges in human neutrophil alpha-defensin 2 on its bactericidal and membrane activity.
Human neutrophil alpha-defensin 2 (HNP2) was N-terminally acetylated and/or C-terminally amidated, resulting in three terminally modified analogs, Ac-HNP2, HNP2-NH2 and Ac-HNP2-NH2. We examined their bactericidal activity against E. coli and S. aureus and their ability to induce leakage from large unilamellar vesicles. Loss of the N-terminal positive charge was functionally deleterious, whereas removal of the C-terminal negative charge enhanced microbial killing and membrane permeabilization. Our findings validate the importance of electrostatic forces in defensin-microbe interactions and point to the bacterial cytoplasmic membrane as a target of HNP2 activity.
Xie
Cao
C
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA.
Zeng
Pengyun
P
Ericksen
Bryan
B
Wu
Zhibin
Z
Lu
Wei-Yue
WY
Lu
Wuyuan
W
D000107:Acetylation; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000254:growth & development*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000254:growth & development*; D023084:alpha-Defensins / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D023084:alpha-Defensins; C406416:human neutrophil peptide 2