Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity.
Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.
Farnaud
Sebastien
S
Randall Centre for Molecular Mechanisms of Cell Function, King's College London, New Hunt's House, Guy's Campus, St. Thomas Street, London SE1 1UL, UK. sebatian.farnaud@kcl.ac.uk
Spiller
Claire
C
Moriarty
Laura C
LC
Patel
Alpesh
A
Gant
Vanya
V
Odell
Edward W
EW
Evans
Robert W
RW
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007781:Lactoferrin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D009842:Oligopeptides; D010743:Phospholipids; C402895:tritrpticin; C082171:lactoferricin B; D007781:Lactoferrin