Cationic cell-penetrating peptide is bactericidal against Neisseria gonorrhoeae

Objectives: Cell-penetrating peptides (CPPs) have been evaluated for intracellular delivery of molecules and several CPPs have bactericidal activity. Our objectives were to determine the effect of a 12 amino acid CPPs on survival and on the invasive and inflammatory potential of Neisseria gonorrhoeae. Methods: Survival of MDR and human challenge strains of N. gonorrhoeae grown in cell culture medium with 10% FBS was determined after treatment with the CPP and human antimicrobial peptide LL-37 for 4h. Confocal microscopy was used to examine penetration of FITC-labelled CPP into bacterial cells. The ability of the CPP to prevent invasion of human ME-180 cervical epithelial cells and to reduce the induction of TNF-alpha in human THP-1 monocytic cells in response to gonococcal infection was assessed. Cytotoxicity of the CPP towards the THP-1 cells was determined. Results: The CPP was bactericidal, with 95%-100% killing of all gonococcal strains at 100 mu M. Confocal microscopy of gonococci incubated with FITC-labelled CPP revealed the penetration of the peptide. CPP treatment of N. gonorrhoeae inhibited gonococcal invasion of ME-180 cells and reduced the expression of TNF-alpha induced in THP-1 cells by gonococci. The CPP showed no cytotoxicity towards human THP-1 cells. Conclusions: Based on these promising results, future studies will focus on testing of CPP in the presence of other types of host cells and exploration of structural modifications of the CPP that could decrease its susceptibility to proteolysis and increase its potency.