title: AdDLP, a bacterial defensin-like peptide, exhibits anti-Plasmodium activity.
abstract: Antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet (CSalphabeta) motif are widely distributed in three eukaryotic kingdoms. However, recent work suggests that bacteria could possess defensin-like peptides (DLPs). Here, we report recombinant expression, in vitro folding, structural and functional characterization of a DLP from the myxobacterium Anaeromyxobacter dehalogenans (AdDLP). Circular dichroism analysis indicates that recombinant AdDLP adopts a typical structural feature of eukaryotic defensins, which is also consistent with an ab initio structure model predicted using I-TASSER algorithm. We found that AdDLP is an antimalarial peptide that led to more than 50% growth inhibition on sexual stages of Plasmodium berghei at micromolar concentrations and killed 100% intraerythrocytic Plasmodium falciparum at 10 microM in a time-dependent manner. These results provide functional evidence for myxobacterial origin of eukaryotic defensins. High-level production of the pure anti-Plasmodium peptide without harming mammalian red blood cells in Escherichia coli makes AdDLP an interesting candidate for antimalarial drug design.
authors.affiliation: Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Rodriguez
authors.forename: Humberto
authors.initials: H
authors.lastname: Lanz-Mendoza
authors.forename: Shunyi
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D023082:Defensins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D015195:Drug Design; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000187:drug effects*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology
chemical_list: C542953:AdDLP protein, Anaeromyxobacter dehalogenans; D000962:Antimalarials; D023082:Defensins; D011994:Recombinant Proteins