ALL libraries (COBIB.SI union bibliographic/catalogue database)
PDF
  • Studies on lactoferricin derived E. coli membrane active peptides reveal differences in the mechanism of N-acylated versus non-acylated peptides [Elektronski vir]
    Zweytick, Dagmar ...
    In order to improve the low antimicrobial activity of LF11, an 11-mer peptide derived from human lactoferricin, mutant sequences were designed based on the defined structure of LF11 in lipidic ... environment. Thereby, deletion of non-charged polar residues and strengthening of the hydrophobic N-terminal part upon adding a bulky hydrophobic amino acid or N-acylation resulted in enhanced antimicrobial activity against E. coli, which correlated with the peptides' degree of perturbation of bacterial membrane mimics. Non-acylated and N-acylated peptides exhibited different effects at a molecular level. Non-acylated peptides induced segregation of peptide-enriched and peptide-poorlipid domains in negatively charged bilayers, while N-acylated peptides formed small heterogeneous domains resulting in a higher degree of packing defects. Additionally, only N-acylated peptides perturbed the lateral packing of neutral lipids and exhibited increased permeability of E. coli lipid vesicles. The latter did not correlate with the extent of improvement ofthe antimicrobial activity, which could be explained by the fact that elevated binding of N-acylated peptides to lipopolysaccharides of the outer membrane of Gram-negative bacteria seems to counteract the elevated membrane permeabilization, reflected in the respective minimal inhibitory concentrationfor E. coli. The antimicrobial activity of the peptides correlated with an increase of membrane curvature stress and hence bilayer instability. Transmission electron microscopy revealed that only the N-acylated peptides induced tubular protrusions from the outer membrane whereas all peptides caused detachment of the outer and inner membrane of E. coli bacteria. Viability tests demonstrated that these bacteria were dead before onset of visible cell lysis.
    Source: Journal of biological chemistry [Elektronski vir]. - ISSN 1083-351X (Vol. 286, no. 24, 2011, str. 21266-21276)
    Type of material - e-article
    Publish date - 2011
    Language - english
    COBISS.SI-ID - 4652826
    DOI

Shelf entry