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

Authors
  • Hair, Pamela S.1
  • Gregory Rivera, Magdielis2
  • Enos, Adrianne I.1
  • Pearsall, Susan E.1
  • Sharp, Julia A.2
  • Yousefieh, Nazita3
  • Lattanzio, Frank A.4
  • Krishna, Neel K.1, 2
  • Cunnion, Kenji M.1, 2, 5, 6
  • 1 Eastern Virginia Medical School, Department of Pediatrics, 700 West Olney Road, Norfolk, VA, 23507, USA , Norfolk (United States)
  • 2 Eastern Virginia Medical School, Department of Microbiology and Molecular Cell Biology, 700 West Olney Road, Norfolk, VA, 23507-1696, USA , Norfolk (United States)
  • 3 Eastern Virginia Medical School, CONRAD, Department of Obstetrics and Gynecology, 700 West Olney Road, Norfolk, VA, 23507, USA , Norfolk (United States)
  • 4 Eastern Virginia Medical School, Department of Physiological Sciences, 700 West Olney Road, Norfolk, VA, 23507, USA , Norfolk (United States)
  • 5 Children’s Specialty Group, 811 Redgate Avenue, Norfolk, VA, 23507, USA , Norfolk (United States)
  • 6 Children’s Hospital of The King’s Daughters, 601 Children’s Lane, Norfolk, VA, 23507, USA , Norfolk (United States)
Type
Published Article
Journal
International Journal of Peptide Research and Therapeutics
Publisher
Springer-Verlag
Publication Date
Nov 29, 2017
Volume
25
Issue
1
Pages
83–92
Identifiers
DOI: 10.1007/s10989-017-9651-z
Source
Springer Nature
Keywords
License
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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.

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