title: Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival.
abstract: BACKGROUND
  Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs) as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages.
  
  
  RESULTS
  An MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model.
  
  
  CONCLUSIONS
  Interestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials.
authors.affiliation: Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, and the Department of Medical Genetics, Vancouver, Canada.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Lynn
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.forename: Alexandra K
authors.initials: AK
authors.lastname: Marr
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
authors.forename: Nelly
authors.initials: N
authors.lastname: Panté
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Elliott
authors.forename: Scott
authors.initials: S
authors.lastname: Napper
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hancock
authors.forename: W Robert
authors.initials: WR
authors.lastname: McMaster
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis; D006801:Humans; D007536:Isomerism; D018320:Leishmania major / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; C102360:BMAP-28; D011506:Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania