Cm-p5: an antifungal hydrophilic peptide derived from the coastal mollusk Cenchritis muricatus (Gastropoda: Littorinidae).
Antimicrobial peptides form part of the first line of defense against pathogens for many organisms. Current treatments for fungal infections are limited by drug toxicity and pathogen resistance. Cm-p5 (SRSELIVHQRLF), a peptide derived from the marine mollusk Cenchritis muricatus peptide Cm-p1, has a significantly increased fungistatic activity against pathogenic Candida albicans (minimal inhibitory concentration, 10 µg/ml; EC50, 1.146 µg/ml) while exhibiting low toxic effects against a cultured mammalian cell line. Cm-p5 as characterized by circular dichroism and nuclear magnetic resonance revealed an α-helical structure in membrane-mimetic conditions and a tendency to random coil folding in aqueous solutions. Additional studies modeling Cm-p5 binding to a phosphatidylserine bilayer in silico and isothermal titration calorimetry using lipid monophases demonstrated that Cm-p5 has a high affinity for the phospholipids of fungal membranes (phosphatidylserine and phosphatidylethanolamine), only moderate interactions with a mammalian membrane phospholipid, low interaction with ergosterol, and no interaction with chitin. Adhesion of Cm-p5 to living C. albicans cells was confirmed by fluorescence microscopy with FITC-labeled peptide. In a systemic candidiasis model in mice, intraperitoneal administration of Cm-p5 was unable to control the fungal kidney burden, although its low amphiphaticity could be modified to generate new derivatives with improved fungicidal activity and stability.
Center for Protein Studies, Faculty of Biology, Havana University, Branch of Parasitology, Institute of Tropical Medicine "Pedro Kourí," and Laboratory of Peptide Analysis and Synthesis, Center of Genetic Engineering and Biotechnology, Havana, Cuba
Carlos
C
López-Abarrategui
Christine
C
McBeth
Santi M
SM
Mandal
Zhenyu J
ZJ
Sun
Gregory
G
Heffron
Annia
A
Alba-Menéndez
Ludovico
L
Migliolo
Osvaldo
O
Reyes-Acosta
Mónica
M
García-Villarino
Diego O
DO
Nolasco
Rosana
R
Falcão
Mariana D
MD
Cherobim
Simoni C
SC
Dias
Wolfgang
W
Brandt
Ludger
L
Wessjohann
Michael
M
Starnbach
Octavio L
OL
Franco
Anselmo J
AJ
Otero-González
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002942:Circular Dichroism / Q000379:methods; D005260:Female; D049851:Gastropoda / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods; D008974:Mollusca / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D017433:Protein Structure, Secondary
D000935:Antifungal Agents; D010455:Peptides; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; C483858:phosphatidylethanolamine
Candida albicans; antimicrobial peptide; systemic candidiasis