title: Trypanosoma cruzi: synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts.
abstract: The parasite Trypanasoma cruzi is responsible for Chagas disease and its triatomine vector, Rhodnius prolixus, has a symbiotic relationship with the soil bacterium, Rhodococcus rhodnii. R. rhodnii that was previously genetically engineered to produce the anti-microbial peptide, cecropin A was co-infected with T. cruzi into R. prolixus resulting in clearance of the infectious T. cruzi in 65% of the vectors. Similar anti-microbial peptides have been isolated elsewhere and were studied for differential toxicity against T. cruzi and R. rhodnii. Of the six anti-microbial peptides tested, apidaecin, magainin II, melittin, and cecropin A were deemed potential candidates for the Chagas paratransgenic system as they were capable of killing T.cruzi at concentrations that exhibit little or no toxic effects on R. rhodnii. Subsequent treatments of T. cruzi with these peptides in pair-wise combinations resulted in synergistic killing, indicating that improvement of the 65% parasite clearance seen in previous experiments may be possible utilizing combinations of different anti-microbial peptides.
authors.affiliation: Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
authors.forename: Annabeth
authors.initials: A
authors.lastname: Fieck
authors.forename: Ivy
authors.initials: I
authors.lastname: Hurwitz
authors.forename: Angray S
authors.initials: AS
authors.lastname: Kang
authors.forename: Ravi
authors.initials: R
authors.lastname: Durvasula
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D014355:Chagas Disease / Q000517:prevention & control* / Q000635:transmission; D004357:Drug Synergism; D020128:Inhibitory Concentration 50; D019476:Insect Proteins / Q000494:pharmacology; D007303:Insect Vectors / Q000382:microbiology / Q000469:parasitology; D054806:Magainins; D008555:Melitten / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D021261:Parasitic Sensitivity Tests; D012239:Rhodnius / Q000382:microbiology / Q000469:parasitology*; D012240:Rhodococcus / Q000187:drug effects* / Q000502:physiology; D013559:Symbiosis; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology; D029867:Xenopus Proteins / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D019476:Insect Proteins; D054806:Magainins; D029867:Xenopus Proteins; C097209:moricin protein, Bombyx mori; C053301:magainin 2 peptide, Xenopus; C061361:apidaecin; D008555:Melitten; C031161:cecropin A