ZL-2, a cathelicidin-derived antimicrobial peptide, has a broad antimicrobial activity against gram-positive bacteria and gram-negative bacteria in vitro and in vivo.

Abstract

Alloferons are a group of naturally occurring peptides primarily isolated from insects that are capable of stimulating mouse and human NK cell cytotoxicity toward cancer cells. In this study, we found that a modified antibacterial peptide had a broad range of action against both gram-positive and gram-negative bacteria. A time-course experiment showed that CFU counts rapidly decreased after ZL-2 treatment, with the bacteria nearly eliminated within 4 h. We also examined the synergy between the peptide and antibiotics. The peptide ZL-2 resulted in a significant synergistic improvement in the potencies of ampicillin, erythromycin and ceftazidime against methicillin-resistant bacteria. In addition, ZL-2 had no detectable cytotoxicity in mouse spleen cells or a mouse animal model. In the mouse model by i.p. inoculation with Escherichia coli, timely treatment of i.p. injection with ZL-2 resulted in 100-fold reduction in bacteria load in blood as well as 80% protection from death in the inoculated animals. In conclusion, we successfully identified a modified peptide with maximal bactericidal activity. This study also provides a potential therapeutic for the treatment of E. coli septicemia by increasing the activity of antimicrobials.