Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1-3 with phospholipids at the air-water interface and inner membrane of E. coli.
Synthetic peptides Phd1-3 spanning the cationic carboxy-terminal region of human beta-defensins HBD-1-3 have been shown to have antibacterial activity. Gross morphological changes were seen in E. coli cells treated with these peptides. In this paper, we have studied the surface-active properties of peptides Phd1-3 and their interactions with different phospholipids using Langmuir-Blodgett monolayers. Compression isotherms and increase in pressure on insertion of peptides into lipid monolayers at different initial pressures indicate the affinity of these peptides for negatively charged lipids. Phd3 inserted less effectively into monolayers as compared to Phd1 and Phd2. The peptides differed in their ability to permeabilize the inner membrane of E. coli, with Phd3 being least effective. It is likely that the peptides kill Gram-negative bacteria by more than one mechanism. When hydrophobicity and net charge favor insertion into lipid membranes, then membrane permeabilization could be the primary event in the killing of bacteria. In cases where membrane insertion does not occur, interaction with phospholipid interface induces highly selective stress that leads to stasis and cell death, as proposed for polymyxin B and bactenecin.
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
Viswanatha
V
Krishnakumari
Ramakrishnan
R
Nagaraj
D000388:Air; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010743:Phospholipids / Q000737:chemistry*; D011312:Pressure; D013997:Time Factors; D014867:Water / Q000737:chemistry; D023083:beta-Defensins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D010743:Phospholipids; D023083:beta-Defensins; D014867:Water