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Peptide Inhibitor of Complement C1 (PIC1) Inhibits Growth of Pathogenic Bacteria

  • Pamela S. Hair
  • Magdielis Gregory Rivera
  • Adrianne I. Enos
  • Susan E. Pearsall
  • Julia A. Sharp
  • Nazita Yousefieh
  • Frank A. Lattanzio
  • Neel K. Krishna
  • Kenji M. CunnionEmail author
Article

Abstract

Peptide Inhibitor of Complement C1 (PIC1) is a family of 15 amino acid peptides that inhibit complement activation via the classical and lectin pathways and inhibit myeloperoxidase. PIC1 peptides were originally derived from a region of limited homology with defensin human neutrophil peptide 1 (HNP-1). Despite having undergone extensive rearrangements of amino acid sequence subsequently, PIC1 peptides retain the defensin-like characteristics of being cysteine rich and amphiphilic. To date, defensin-like antimicrobial activity for PIC1 has not been explored. Here we report the antimicrobial activity of PIC1 for multiple pathogenic bacteria tested in minimum inhibitory concentration (MIC)-type assays. PIC1variant PA-dPEG24 was found to have antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Neisseria meningitidis, Neisseria gonorrhoeae, Gardnerella vaginalis, and Prevotella bivia. Confocal microscopy demonstrated PIC1 localized to the surface of P. aeruginosa and S. aureus consistent with the defensins. Testing PIC1 variants with amino acid substitutions revealed differences in complement inhibition and antimicrobial effects suggesting these occur via independent mechanisms. PIC1 inhibited P. aeruginosa growth in normal human serum suggesting the antimicrobial effect was dominant versus the survival benefit resulting from complement inhibition. In summary, these experiments demonstrate that PIC1 peptides have broad antimicrobial activity against pathogenic bacteria similar to defensins.

Keywords

Defensin Antibiotic Complement Staphylococcus Pseudomonas Neisseria 

Notes

Acknowledgements

This work was supported in part by grants from Eastern Virginia Medical School and the Children’s Health Foundation (The Children’s Hospital of The King’s Daughters). Advice for certain bacterial growth conditions was kindly provided by the Clinical Microbiology Laboratory staff of The Children’s Hospital of The King’s Daughters and Dr. Dayle Daines at Old Dominion University.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Pamela S. Hair
    • 1
  • Magdielis Gregory Rivera
    • 2
  • Adrianne I. Enos
    • 1
  • Susan E. Pearsall
    • 1
  • Julia A. Sharp
    • 2
  • Nazita Yousefieh
    • 3
  • Frank A. Lattanzio
    • 4
  • Neel K. Krishna
    • 1
    • 2
  • Kenji M. Cunnion
    • 1
    • 2
    • 5
    • 6
    Email author
  1. 1.Department of PediatricsEastern Virginia Medical SchoolNorfolkUSA
  2. 2.Department of Microbiology and Molecular Cell BiologyEastern Virginia Medical SchoolNorfolkUSA
  3. 3.CONRAD, Department of Obstetrics and GynecologyEastern Virginia Medical SchoolNorfolkUSA
  4. 4.Department of Physiological SciencesEastern Virginia Medical SchoolNorfolkUSA
  5. 5.Children’s Specialty GroupNorfolkUSA
  6. 6.Children’s Hospital of The King’s DaughtersNorfolkUSA

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