Antimicrobial activity of a 13 amino acid tryptophan-rich peptide derived from a putative porcine precursor protein of a novel family of antibacterial peptides.
It has long been speculated that porcine cathelin is an N-terminal fragment of a longer precursor protein which possesses antimicrobial activity. In an attempt to find such a precursor, a cDNA clone was recently isolated and sequenced by screening a cDNA library from porcine bone marrow. In order to identify the functional activity of the putative protein encoded by an open reading frame, we have synthesized various lengths of peptides that correspond to the C-terminal region of the protein and examined them for their antimicrobial activities. We found that a 13 amino acid tryptophan-rich region with the sequence of VRRFPWWWPFLRR had strong antimicrobial activity with a wide spectrum. It showed potency against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Staphylococcus epidermidis, Proteus mirabilis, and Streptococcus group D as well as Aspergillus fumigatus. The action of this peptide is bactericidal rather than bacteriostatic and this activity is completely inhibited by 2 mM MgCl2. Our results indicate that the previously identified putative precursor encoded by the isolated cDNA indeed possesses a potent antimicrobial activity and that this 13 amino acid synthetic peptide is considered to be a potentially effective drug against various infectious agents.
Lawyer
C
C
Department of Internal Medicine Pulmonary Division, School of Medicine, Southern Illinois University, Springfield 62702, USA.
Pai
S
S
Watabe
M
M
Borgia
P
P
Mashimo
T
T
Eagleton
L
L
Watabe
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001232:Aspergillus fumigatus / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects*; D001853:Bone Marrow; D002118:Calcium / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D018076:DNA, Complementary; D004926:Escherichia coli / Q000187:drug effects; D015723:Gene Library; D007711:Klebsiella pneumoniae / Q000187:drug effects; D015636:Magnesium Chloride / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology*; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011513:Proteus mirabilis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013552:Swine; D014364:Tryptophan
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D018076:DNA, Complementary; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; C084515:cathelin; D015636:Magnesium Chloride; D014364:Tryptophan; D002118:Calcium