Killing of African trypanosomes by antimicrobial peptides.
Antimicrobial peptides are components of the innate immune systems of a wide variety of eukaryotic organisms and are being developed as antibiotics in the fight against bacterial and fungal infections. We explored the potential activities of antimicrobial peptides against the African trypanosome Trypanosoma brucei, a vector-borne protozoan parasite that is responsible for significant morbidity and mortality in both humans and animals. Three classes of mammalian antimicrobial peptides were tested: alpha-defensins, beta-defensins, and cathelicidins. Although members of all 3 classes of antimicrobial peptides showed activity, those derived from the cathelicidin class were most effective, killing both insect and bloodstream forms of the parasite. The mechanism of action of the cathelicidins against T. brucei involves disruption of surface membrane integrity. Administration of cathelicidin antimicrobial peptides to mice with late-stage T. brucei infection acutely decreased parasitemia and prolonged survival. These results highlight the potential use of antimicrobial peptides for the treatment of African trypanosomiasis.
McGwire
Bradford S
BS
Departments of Pathology and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, and Section of Infectious Diseases, College of Medicine, University of Illinois, Chicago, Illinois, USA. b-mcgwire@northwestern.edu
Olson
Cheryl L
CL
Tack
Brian F
BF
Engman
David M
DM
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D054804:Cathelicidins; D002462:Cell Membrane / Q000187:drug effects; D006801:Humans; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D014352:Trypanosomiasis / Q000188:drug therapy; D023084:alpha-Defensins / Q000494:pharmacology*; D023083:beta-Defensins / Q000494:pharmacology*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D023084:alpha-Defensins; D023083:beta-Defensins