Protozoan parasites are the causative agent of much disease in tropical areas of the world. Currently, the control of these diseases is dependent on outdated drug treatment, with associated high toxicity and drug resistance. There is an urgent need for novel anti-parasitic therapies. One emerging anti-parasitic therapies is Host defence peptides (HDPs). Here we test the HDP BMAP-28 as an anti-leishmanial therapy against two lifecycle stages of Leishmania major, the promastigotes (insect infective form) and the intracellular amastigote (mammalian infective form). Two stereoisomers of BMAP-28, the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), were also tested for anti-leishmanial activity. The BMAP-28 form (L-form) was susceptible to degradation by GP63, the metalloproteinase that covers the promastigotes cell surface. However, the BMAP-28 isomers, the D-form and RI-form were resistant, and therefore more potent against the promastigote parasite. Though other anti-leishmanial HDP studies focus on the promastigote form of the parasite, it is the mammalian infective form, the amastigote, which causes the disease symptoms. Here we demonstrate that BMAP-28 and its isomers D-BMAP-28 and RI-BMAP-28 are effective against the amastigote form of the parasite using a macrophage infection model. These findings show that BMAP-28 has excellent potential as a novel anti-leishmanial therapeutic
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