Characterization of Antimicrobial and Host-Defense Peptides by NMR Spectroscopy

  • Hans J. Vogel
  • Mauricio Arias
  • James M. Aramini
  • Subrata Paul
  • Zhihong Liu
  • Hiroaki Ishida
Reference work entry

Abstract

The mammalian innate immune system relies on a series of cationic antimicrobial peptides and various host-defense proteins to ward of invasions by pathogenic bacteria. NMR spectroscopy has played a dominant role in identifying the amphipathic three-dimensional structures of antimicrobial peptides and gaining an understanding of their mechanism of action. Most studies to date have relied on regular proton NMR approaches, but multidimensional NMR studies of carbon-13 and nitrogen-15 isotope-labeled peptides, as well as fluorine-19 NMR, are now commonly used as well. While the majority of the cationic antimicrobial peptides can give rise to bacterial killing by selectively perturbing the negatively charged bacterial membranes, others enter the cell and act on intracellular protein targets or nucleic acids. Some host defense proteins create ‘nutritional immunity’, by binding essential metal ions, such as iron or zinc, while others can enzymatically degrade bacterial peptidoglycan in the cell envelope. In response, several pathogenic bacteria have developed various defense mechanisms, involving the alteration of their membrane surface charge, or expression of unique proteins that can intercept antimicrobial peptides or host defense proteins. NMR spectroscopy has also played a major role in characterizing the protein-protein or protein-peptide complexes that play a role in these processes. Finally, NMR metabolomics and MRI imaging approaches have been deployed to study the mode of action of antibiotics and antimicrobial peptides in animal models and hopefully in the future these techniques can be used to determine their efficacy in human patients.

Keywords

Amphipathic structures Anticancer peptides Antimicrobial peptides Host-defense peptides Innate immunity Isotope labeling NMR structures Solvent perturbation 

Notes

Acknowledgments

Research on antimicrobial peptides and host-defense proteins in the authors’ laboratory was supported by a “Novel alternatives to antibiotics” operating team grant from the Canadian Institutes for Health Research and by a CRIO grant from Alberta Innovates Health Solutions.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Hans J. Vogel
    • 1
  • Mauricio Arias
    • 1
  • James M. Aramini
    • 2
  • Subrata Paul
    • 1
  • Zhihong Liu
    • 1
  • Hiroaki Ishida
    • 1
  1. 1.Bio-NMR Centre, Department of Biological SciencesUniversity of CalgaryCalgaryCanada
  2. 2.Structural Biology InitiativeCity University of New YorkNew YorkUSA

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