title: Influence of N-acylation of a peptide derived from human lactoferricin on membrane selectivity.
abstract: Increasing numbers of bacterial strains being resistant to conventional antibiotics emphasize the urgent need for new antimicrobial agents. One strategy is based on host defence peptides that can be found in every organism including humans. We have studied the antimicrobial peptide LF11, derived from the pepsin cleavage product of human lactoferrin, known for its antimicrobial and lipid A-binding activity, and peptide C12LF11, the N-lauryl-derivative of LF11, which has owing to the attached hydrocarbon chain an additional hydrophobic segment. The influence of this hydrocarbon chain on membrane selectivity was studied using model membranes composed of dipalmitoylphosphatidylglycerol (DPPG), mimicking bacterial plasma membranes, and of dipalmitoylphosphatidylcholine (DPPC), a model system for mammalian membranes. A variety of biophysical techniques was applied. Thereby, we found that LF11 did not affect DPPC bilayers and showed only moderate effects on DPPG membranes in accordance with its non-hemolytic and weak antimicrobial activity. In contrast, the introduction of the N-lauryl group caused significant changes in the phase behaviour and lipid chain packing in both model membrane systems. These findings correlate with the in vitro tests on methicillin resistant S. aureus, E. coli, P. aeruginosa and human red blood cells, showing increased biological activity of C12LF11 towards these test organisms. This provides evidence that both electrostatic and hydrophobic interactions are crucial for biological activity of antimicrobial peptides, whereas a certain balance between the two components has to be kept, in order not to loose the specificity for bacterial membranes.
authors.affiliation: Institute of Biophysics and X-ray Structure Research, Austrian Academy of Sciences, Schmiedlstrasse 6, A-8042 Graz, Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zweytick
authors.forename: Georg
authors.initials: G
authors.lastname: Pabst
authors.forename: Peter M
authors.initials: PM
authors.lastname: Abuja
authors.forename: Alexander
authors.initials: A
authors.lastname: Jilek
authors.forename: Sylvie E
authors.initials: SE
authors.lastname: Blondelle
authors.forename: Jörg
authors.initials: J
authors.lastname: Andrä
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
authors.forename: Daniel
authors.initials: D
authors.lastname: Monreal
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martinez de Tejada
authors.forename: Karl
authors.initials: K
authors.lastname: Lohner
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D010455:Peptides; C082171:lactoferricin B; D007781:Lactoferrin