Repurposing a drug targeting peptide for targeting antimicrobial peptides against Staphylococcus
Targeted therapies seek to selectively eliminate a pathogen without disrupting the resident microbial community. However, with selectivity comes the potential for developing bacterial resistance. Thus, a diverse range of targeting peptides must be made available.
Two commonly used antimicrobial peptides (AMPs), plectasin and eurocin, were genetically fused to the targeting peptide A12C, which selectively binds to Staphylococcus species. The targeting peptide did not decrease activity against the targeted Staphylococcus aureus and Staphylococcus epidermidis, but drastically decreased activity against the nontargeted species, Enterococcus faecalis, Bacillus subtilis, Lactococcus lactis and Lactobacillus rhamnosus. This effect was equally evident across two different AMPs, two different species of Staphylococcus, four different negative control bacteria, and against both biofilm and planktonic forms of the bacteria.
A12C, originally designed for targeted drug delivery, was repurposed to target antimicrobial peptides. This illustrates the wealth of ligands, both natural and synthetic, which can be adapted to develop a diverse array of targeting antimicrobial peptides.
KeywordsAntimicrobial peptides Phage peptide display Staphylococcus SUMO Targeted
Matthew Cranford from the Trakselis Laboratory at Baylor assisted with protein purification and the Baylor Mass Spectrometry Center provided support for our mass spectrometry analysis.
Supplementary File 1—Supplementary Figs. 1 to 11 and Table 1.
All authors contributed to the design of the project. AC, SI and MG built the genetic constructs and performed the protein purification and analysis. AC and MG did the microbial inhibition determinations. AC, SI, MG and CK wrote the manuscript. All authors read and approved the final manuscript. CK supervised each stage of the experiment.
This work was funded by a University Research Committee (URC) grant provided by Baylor University [Grant No. KU-2015]. The design, implementation and data interpretation are solely the product of the authors.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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