AdDLP, a bacterial defensin-like peptide, exhibits anti-Plasmodium activity.
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.
Gao
Bin
B
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.
Rodriguez
Maria del Carmen
Mdel C
Lanz-Mendoza
Humberto
H
Zhu
Shunyi
S
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
C542953:AdDLP protein, Anaeromyxobacter dehalogenans; D000962:Antimalarials; D023082:Defensins; D011994:Recombinant Proteins