Preliminary antimicrobial activity of CT-K3K7, a modified peptide by lysine substitutions from scorpion venom peptide

Abstract Antimicrobial peptides (AMPs) have gained interest as a new type of antimicrobial agent. Scorpion venom peptide ctry2459 were modified to CT-K3K7 by lysine substitutions at position 3rd and 7th. We found that the modified peptides CT-K3K7 with improved antibacterial activity, higher thermal stability and lower hemolytic activity. It can rapidly kill S. aureus and P. aeruginosa, reduce the production of biofilm and live bacteria residues in biofilm in vitro. CT-K3K7 has also been demonstrated that could decrease the bacterial counts in the subcutaneous abscess region, abscess area, and inflammatory cell infiltration in mouse subcutaneous abscess models duplicated by S. aureus and P. aeruginosa. CT-K3K7 is difficult to induce S. aureus and P. aeruginosa to develop drugs resistance, which may be related to the bactericidal way that the increase of cationic properties by lysine substitutions can increase the electrostatic force between the peptides and the bacterial surface that lead to the increase of bacterial membrane permeability and DNA binding. In conclusion, the modified peptide CT-K3K7 enhanced antimicrobial activity and can be as a new antimicrobial agent candidate for the treatment of infections by S. aureus and P. aeruginosa.