Identification of antimicrobial peptide regions derived from genomic sequences of phage lysins.
This study was designed to test the possibility that antimicrobial peptides could be derived from the genomic sequences of phage lysins. Using two lysins (D3 and PhiKZ) we selected and produced two putative peptides (X and Z, respectively) believed to possess antimicrobial properties based on their physicochemical characteristics. The data presented support this hypothesis in that the peptides and various analogs displayed antibacterial activity, bacteriostatic or bactericidal, either individually or upon combination. These putative peptides are believed to act by a mechanism of action resembling that of conventional antimicrobial peptides when judged by both structural and functional criteria. Thus, the peptides are shown to have the ability to form a helical structure, to bind to model bacterial membranes and permeabilize model liposomes. They also display rapid bactericidal kinetics and their antibacterial potency is increased upon amidation. The possible relevance of these results in contributing to potency of phage lysins is discussed. Such peptides may be used to design new potent antimicrobial compounds much needed in face of the ever threatening drug resistance problems.
Rotem
Shahar
S
Laboratory of Antimicrobial Investigation (LAPI), Department of Biotechnology & Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
Radzishevsky
Inna
I
Inouye
Roger T
RT
Samore
Matthew
M
Mor
Amram
A
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D001433:Bacteriolysis / Q000235:genetics*; D016679:Genome, Viral; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics* / Q000494:pharmacology; D017105:Pseudomonas Phages / Q000201:enzymology* / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics; D020539:Sequence Analysis, Protein
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010446:Peptide Fragments