The use of a virus-derived targeting peptide to selectively kill staphylococcus bacteria with antimicrobial peptides

Abstract

BackgroundTargeted therapies seek to selectively eliminate a pathogen without disrupting the microbiome community. Bacteriophages provide a rich, well-documented source of bacterium-specific binding proteins for use as targeting peptides fused to antimicrobial peptides. Though resistance may develop as with any antibiotic, the wealth of variants available in natural bacteriophage populations adds to the robustness of this system.\n\nResultsHere, we target two cationic antimicrobial peptides (AMPs), plectasin and eurocin, by genetically fusing their coding sequence to that of the host-binding protein of bacteriophage A12C, which selectively infects Staphylococcus. Surprisingly, we noted that targeting brought no change in the toxicity of the AMP when applied to two different staphylococci, S. aureus and S. epidermidis, but found a drastic decrease in toxicity against the negative controls, Enterococcus faecalis and Bacillus subtilis. Thus, the differential selectivity in this case is a loss of toxicity against the non-target species rather than the gain of toxicity against the target species which was reported in previous studies with other types of targeting antimicrobial peptides.\n\nConclusionThis is the first report of the use of virus-derived peptide sequences to target antimicrobial peptides. Considering the very large databank of bacteriophages and their bacterial hosts, this targeting approach should be generally applicable to a wide range of bacterial pathogens.