Repurposing a drug targeting peptide for targeting antimicrobial peptides against Staphylococcus

  • Ankan Choudhury
  • S. M. Ashiqul Islam
  • Meron R. Ghidey
  • Christopher Michel KearneyEmail author
Original Research Paper



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.


Antimicrobial 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.

Supporting information

Supplementary File 1—Supplementary Figs. 1 to 11 and Table 1.

Author contributions

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.

Supplementary material

10529_2019_2779_MOESM1_ESM.docx (727 kb)
Supplementary file1 (DOCX 727 kb)


  1. Dowah ASA, Clokie MRJ (2018) Review of the nature, diversity and structure of bacteriophage receptor binding proteins that target Gram-positive bacteria. Biophys Rev 10:535–542. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Eckert R, He J, Yarbrough DK et al (2006) Targeted killing of Streptococcus mutans by a pheromone-guided “smart” antimicrobial peptide. Antimicrob Agents Chemother 50:3651–3657. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Eckert R, Sullivan R, Shi W (2012) Targeted antimicrobial treatment to re-establish a healthy microbial flora for long-term protection. Adv Dent Res 24:94–97. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Evans BC, Nelson CE, Yu SS et al (2013) Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J Vis Exp. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Islam SMA, Sajed T, Kearney CM, Baker EJ (2015) PredSTP: a highly accurate SVM based model to predict sequential cystine stabilized peptides. BMC Bioinform 16:210. CrossRefGoogle Scholar
  6. Islam SMA, Kearney CM, Baker EJ (2017) CSPred: a machine-learning-based compound model to identify the functional activities of biologically-stable toxins. In: 2017 IEEE international conference on bioinformatics and biomedicine (BIBM). pp 2254–2255Google Scholar
  7. Li C, Blencke H-M, Paulsen V et al (2010) Powerful workhorses for antimicrobial peptide expression and characterization. Bioeng Bugs 1:217–220. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Li Z, Wang X, Wang X et al (2017) Research advances on plectasin and its derivatives as new potential antimicrobial candidates. Process Biochem 56:62–70. CrossRefGoogle Scholar
  9. Mao R, Teng D, Wang X et al (2013) Design, expression, and characterization of a novel targeted plectasin against methicillin-resistant Staphylococcus aureus. Appl Microbiol Biotechnol 97:3991–4002. CrossRefPubMedGoogle Scholar
  10. Monnet V, Juillard V, Gardan R (2016) Peptide conversations in Gram-positive bacteria. Crit Rev Microbiol 42:339–351. CrossRefPubMedGoogle Scholar
  11. Mygind PH, Fischer RL, Schnorr KM et al (2005) Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature 437:975–980. CrossRefPubMedGoogle Scholar
  12. Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29:464–472. CrossRefGoogle Scholar
  13. Nobrega FL, Vlot M, de Jonge PA et al (2018) Targeting mechanisms of tailed bacteriophages. Nat Rev Microbiol 16:760–773. CrossRefPubMedGoogle Scholar
  14. O’Toole GA (2011) Microtiter dish biofilm formation assay. J Vis Exp. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Oeemig JS, Lynggaard C, Knudsen DH et al (2012) Eurocin, a new fungal defensin: structure, lipid binding, and its mode of action. J Biol Chem 287:42361–42372. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Parachin NS, Mulder KC, Viana AAB et al (2012) Expression systems for heterologous production of antimicrobial peptides. Peptides 38:446–456. CrossRefPubMedGoogle Scholar
  17. Peschel A, Sahl H-G (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4:529–536. CrossRefPubMedGoogle Scholar
  18. Weber-Dąbrowska B, Jończyk-Matysiak E, Żaczek M et al (2016) Bacteriophage procurement for therapeutic purposes. Front Microbiol 7:1177–1177. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Worthington RJ, Melander C (2013) Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol 31:177–184. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Wu C-H, Liu I-J, Lu R-M, Wu H-C (2016) Advancement and applications of peptide phage display technology in biomedical science. J Biomed Sci. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Yacoby I, Shamis M, Bar H et al (2006) Targeting antibacterial agents by using drug-carrying filamentous bacteriophages. Antimicrob Agents Chemother 50:2087–2097. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Institute of Biomedical StudiesBaylor UniversityWacoUSA
  2. 2.Department of BiologyBaylor UniversityWacoUSA

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