Synthetic epidermicin NI01 can protect Galleria mellonella larvae from infection with Staphylococcus aureus

Abstract

OBJECTIVES: Epidermicin is a novel antimicrobial peptide that has potent activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, and it may have potential for use in therapy for infections caused by these bacteria, though in vivo efficacy needs to be demonstrated. Galleria mellonella larvae have recently been introduced as an alternative in vivo model to mammalian systems and here we examined the ability of a synthetic version of epidermicin to protect G. mellonella larvae from infection with S. aureus strains. METHODS: G. mellonella larvae were infected with ∼2.5 × 10(6) cells per larva and then treated with vancomycin or epidermicin and survival recorded over a 120 h period. Vancomycin was used at up to 50 mg/kg and epidermicin at up to 200 mg/kg with administration of treatments occurring 0-2 h post-infection. RESULTS: Epidermicin was shown to be non-toxic and did not stimulate the G. mellonella immune system. When administered 2 h post-infection at a maximum dose of 200 mg/kg, epidermicin significantly increased survival in larvae; however, altering the dosage regimen by reducing the time to administration to 30 min post-infection increased the potency of the peptide. CONCLUSIONS: This is the first report of antimicrobial activity of an artificially synthesized peptide from the type IIc bacteriocin family. The novel peptide protects G. mellonella larvae from infection with both methicillin-susceptible and -resistant S. aureus, although the pharmacodynamic properties are not yet optimal.