Abstract
Smp24 and Smp43 are novel cationic AMPs identified from the venom of the Egyptian scorpion Scorpio maurus palmatus, having potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards three non-tumour cell lines (CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HACAT (human skin keratinocytes) and two acute leukaemia cell lines (myeloid (KG1a) and lymphoid (CCRF-CEM) leukaemia cell lines) using a combination of biochemical and imaging techniques. Smp24 and Smp43 (4–256 µg/mL) decreased the cell viability (as measured by intracellular ATP) of all cells tested, although keratinocytes were markedly less sensitive. Cell membrane leakage as evidenced by the release of lactate dehydrogenase was evident throughout and was confirmed by scanning electron microscope studies.
Highlights
Over the last decades, an increasing number of pathogenic microorganisms have developed resistance to conventional antibiotics posing problems in the management of infection
Scorpion venoms have provided a rich source of Antimicrobial peptides (AMPs) and the possibilities of developing their therapeutic potential is enhanced when it can be demonstrated that such peptides have limited cytotoxic effects on mammalian cells
Smp24 or Smp43 and cellular ATP levels measured with a Cell TitreGlo assay
Summary
An increasing number of pathogenic microorganisms have developed resistance to conventional antibiotics posing problems in the management of infection. Abdel-Rahman et al (2013) identified two novel amphipathic cationic AMPs (Smp and Smp24) through cDNA sequencing of the venom gland of the Egyptian scorpion Scorpio maurus palmatus. Both peptides showed a potent activity against both Gram-positive and Gram-negative bacteria as well as fungi (Harrison et al 2016a) and formed pores in model prokaryotic and eukaryotic phospholipid membranes. The mechanism of membrane disruption caused by Smp depended on phospholipid composition; the peptide formed toroidal pores in prokaryotic-like membranes but hexagonal phase non-lamellar phase structures were seen in eukaryotic-like membranes (Harrison et al 2016b). We have set out to study the cytotoxic effects of Smp and Smp on non-tumour (hematopoietic stem cells, primary renal cells and immortalised keratinocytes) and tumour (myeloid and lymphoid leukaemia) eukaryotic cells lines
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