Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo.
Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo.
复制标题
合成肽 RP-1 和 AA-RP-1 对利什曼原虫的体外和体内功效。
DOI：
10.1128/aac.05349-11
复制
发表时间：
2012
影响因子：
4.9
通讯作者：
Craft,Noah
中科院分区：
文献类型：
--
作者：
Erfe,MarieCriselB;David,ConsueloV;Huang,Cher;Lu,Victoria;Maretti-Mira,AnaClaudia;Haskell,Jacquelyn;Bruhn,KevinW;Yeaman,MichaelR;Craft,Noah
Host defense peptides are naturally occurring molecules that play essential roles in innate immunity to infection. Based on prior structure-function knowledge, we tested two synthetic peptides (RP-1 and AA-RP-1) modeled on the conserved, microbicidal α-helical domain of mammalian CXCL4 platelet kinocidins. These peptides were evaluated for efficacy against Leishmania species, the causative agents of the group of diseases known as leishmaniasis.In vitroantileishmanial activity was assessed against three distinct Leishmania strains by measuring proliferation, metabolic activity and parasite viability after exposure to various concentrations of peptides. We demonstrate that micromolar concentrations of RP-1 and AA-RP-1 caused dose-dependent growth inhibition of Leishmania promastigotes. This antileishmanial activity correlated with rapid membrane disruption, as well as with a loss of mitochondrial transmembrane potential. In addition, RP-1 and AA-RP-1 demonstrated distinct and significantin vivoantileishmanial activities in a mouse model of experimental visceral leishmaniasis after intravenous administration. These results establish efficacy of RP-1 lineage synthetic peptides against Leishmania speciesin vitroand after intravenous administrationin vivoand provide further validation of proof of concept for the development of these and related systemic anti-infective peptides targeting pathogens that are resistant to conventional antibiotics.
