Candidacidal activity of synthetic peptides based on the antimicrobial domain of the neutrophil-derived protein, CAP37.
The primary bactericidal domain of CAP37, a cationic antimicrobial protein with potent activity against Gram-negative organisms was previously shown to reside between amino acids 20 through 44 (NQGRHFCGGALIHARFVMTAASCFQ) of the native protein. In this study, we explored the efficacy of four synthetic CAP37 peptide analogs, based on this sequence, against various Candida species including fluconazole-sensitive and -resistant isolates of C. albicans. Three of the peptides demonstrated strong antifungal activity for C. albicans, including fluconazole-resistant isolates of C. albicans and were active against C. guilliermondii, C. tropicalis, C. pseudotropicalis, C. parapsilosis, and C. dubliniensis. The peptides were ineffective against C. glabrata, C. krusei, and Saccharomyces cerevisiae. For C. albicans isolates, the peptides had relatively greater activity against blastoconidia than hyphal forms, although strong antifungal activity was observed with pseudohyphal forms of the various Candida species tested. Kinetic studies demonstrated fungicidal rather than fungistatic activity. These findings indicate that synthetic peptides based on the antimicrobial domain of CAP37 also have activity against eukaryotic organisms suggesting a broader range of activity than originally demonstrated and show for the first time their potent fungicidal activity.
Pereira
H Anne
HA
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126, USA. anne-pereira@ouhsc.edu
Tsyshevskaya-Hoover
Irina
I
Hinsley
Heather
H
Logan
Sreemathi
S
Nguyen
Melissa
M
Nguyen
Thuy-Trang
TT
Pohl
Jan
J
Wozniak
Karen
K
Fidel
Paul L
PL
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D001798:Blood Proteins / Q000737:chemistry*; D002175:Candida / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D002352:Carrier Proteins / Q000737:chemistry*; D015169:Colony Count, Microbial; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
C062991:AZU1 protein, human; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D010455:Peptides; D015725:Fluconazole