Effects of lactoferrin derived peptides on simulants of biological warfare agents.
Lactoferrin (LF) is an important immune protein in neutrophils and secretory fluids of mammals. Bovine LF (bLF) harbours two antimicrobial stretches, lactoferricin and lactoferampin, situated in close proximity in the N1 domain. To mimic these antimicrobial domain parts a chimeric peptide (LFchimera) has been constructed comprising parts of both stretches (LFcin17-30 and LFampin265-284). To investigate the potency of this construct to combat a set of Gram positive and Gram negative bacteria which are regarded as simulants for biological warfare agents, the effect on bacterial killing, membrane permeability and membrane polarity were determined in comparison to the constituent peptides and the native bLF. Furthermore we aimed to increase the antimicrobial potency of the bLF derived peptides by cationic amino acid substitutions. Overall, the bactericidal activity of the peptides could be related to membrane disturbing effects, i.e. membrane permeabilization and depolarization. Those effects were most prominent for the LFchimera. Arginine residues were found to be crucial for displaying antimicrobial activity, as lysine to arginine substitutions resulted in an increased antimicrobial activity, affecting mostly LFampin265-284 whereas arginine to lysine substitutions resulted in a decreased bactericidal activity, predominantly in case of LFcin17-30.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA, Amsterdam, The Netherlands.
Tjitske
T
Sijbrandij
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA, Amsterdam, The Netherlands.
Antoon J
AJ
Ligtenberg
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA, Amsterdam, The Netherlands.
Kamran
K
Nazmi
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA, Amsterdam, The Netherlands.
Enno C I
EC
Veerman
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA, Amsterdam, The Netherlands.
Jan G M
JG
Bolscher
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA, Amsterdam, The Netherlands. fbikker@acta.nl.
Floris J
FJ
Bikker
D019943:Amino Acid Substitution; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D054045:Biological Warfare Agents; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007781:Lactoferrin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D054045:Biological Warfare Agents; D010446:Peptide Fragments; C502040:lactoferrampin; C082171:lactoferricin B; D007781:Lactoferrin
Antimicrobial activity; Antimicrobial peptide; Biowarfare simulants; LFchimera; Lactoferrin