Hp1404, a New Antimicrobial Peptide from the Scorpion Heterometrus petersii

Abstract

Antimicrobial peptides have attracted much interest as a novel class of antibiotics against a variety of microbes including antibiotics resistant strains. In this study, a new cationic antimicrobial peptide Hp1404 was identified from the scorpion Heterometrus petersii, which is an amphipathic α-helical peptide and has a specific inhibitory activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Hp1404 can penetrate the membrane of S. aureus at low concentration, and disrupts the cellular membrane directly at super high concentration. S. aureus does not develop drug resistance after multiple treatments with Hp1404 at sub MIC concentration, which is possibly associated with the antibacterial mechanism of the peptide. In addition, Hp1404 has low toxicity to both mammalian cells (HC50 = 226.6 µg/mL and CC50 > 100 µg/mL) and balb-c mice (Non-toxicity at 80 mg/Kg by intraperitoneal injection and LD50 = 89.8 mg/Kg by intravenous injection). Interestingly, Hp1404 can improve the survival rate of the MRSA infected balb-c mice in the peritonitis model. Taken together, Hp1404 may have potential applications as an antibacterial agent.

Design, expression, and characterization of the hybrid antimicrobial peptide T‐catesbeianin‐1 based on FyuA

“…Fresh human red blood cells (hRBCs) were obtained from a healthy donor. The hemolytic activity of T‐catesbeianin‐1 was determined according to a previously described protocol . Further, 0.9% saline and 1% Triton X‐100 were served as negative and positive controls, respectively.…”

Protein aggregation as an antibiotic design strategy

“…The ultrathin section of bacteria showed intact membranes without inner pores or obvious perturbations commonly observed with detergent‐acting or carpet‐like AMPs (Yeaman and Yount, ) (http://onlinelibrary.wiley.com/doi/10.1111/mmi.13269/suppinfo). Further, contrary to what is observed upon treatment with cationic α‐helical and amphiphilic AMPs (Anderson et al ., ; Hartmann et al ., ; Li et al ., ), no significant cytoplasmic leakage from the membrane could be observed (http://onlinelibrary.wiley.com/doi/10.1111/mmi.13269/suppinfo). Scanning electron microscopy (SEM) revealed small cell wall irregularities [previously defined as blebs or craters (Hartmann et al ., )] after 15 min that became more obvious and were accompanied by a small (10%) reduction of the cell diameter after 30 min and 1 h (http://onlinelibrary.wiley.com/doi/10.1111/mmi.13269/suppinfo).…”

Insights into Antimicrobial Peptides from Spiders and Scorpions

“…They showed broad-spectrum antibacterial activity. Interestingly, ctriporin, Hp1404, and stigmurin are solely active against Gram-positive bacteria [45,79,80]. Hp1404, isolated from Heterometrus petersii , is an amphipathic α-helical peptide with activity against Gram-positive bacteria including MRSA.…”

“…Hp1404 can penetrate the membrane of S. aureus at a low concentration, and disrupts the cellular membrane directly at high concentrations. In vivo , hp1404 can improve the survival rate of the MRSA infected balb-c mice in the peritonitis model [80]. Stigmurin was selected based on a transcriptomic analysis of the Brazilian yellow scorpion Tityus stigmurus venom gland.…”

“…The first helical model is longer, allowing for two structural and functional regions (Figure 1, A–D), while the second helical model is short, leading to a broad hydrophobic surface with few basic residues (Figure 1G). Long helical peptides rich in basic amino acids usually have a broad activity spectrum, while those short helices poor in basic amino acids tend to be active primarily against Gram-positive bacteria such as S. aureus [45,79,80,103]. These structural models explain the dominance of helical structures in spiders and scorpions and shed light on their cytotoxicity.…”