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Antimicrobial effects of helix D-derived peptides of human antithrombin III.

Papareddy, Praveen LU ; Kalle, Martina LU ; Bhongir, Ravi LU ; Mörgelin, Matthias LU ; Malmsten, Martin and Schmidtchen, Artur LU (2014) In Journal of Biological Chemistry 289(43). p.29790-29800
Abstract
Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix D-derived, peptide FFFAKLNCRL-YRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria... (More)
Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix D-derived, peptide FFFAKLNCRL-YRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Fluorescence microscopy and electron microscopy studies demonstrated that FFF21 binds to, and permeabilizes, bacterial membranes. Analogously, FFF21 was found to induce membrane leakage of model anionic liposomes. In vivo, FFF21 significantly reduced P. aeruginosa infection in mice. Additionally, FFF21 displayed anti-endotoxic effects in vitro. Taken together, our results suggest novel roles for ATIII-derived peptide fragments in host defense. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
289
issue
43
pages
29790 - 29800
publisher
ASBMB
external identifiers
  • pmid:25202017
  • wos:000344370800025
  • scopus:84908408991
ISSN
1083-351X
DOI
10.1074/jbc.M114.570465
language
English
LU publication?
yes
id
9c4f155e-f139-4e64-a91f-d7f7a37eff61 (old id 4691989)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25202017?dopt=Abstract
date added to LUP
2014-10-04 21:37:10
date last changed
2017-06-11 03:13:09
@article{9c4f155e-f139-4e64-a91f-d7f7a37eff61,
  abstract     = {Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix D-derived, peptide FFFAKLNCRL-YRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Fluorescence microscopy and electron microscopy studies demonstrated that FFF21 binds to, and permeabilizes, bacterial membranes. Analogously, FFF21 was found to induce membrane leakage of model anionic liposomes. In vivo, FFF21 significantly reduced P. aeruginosa infection in mice. Additionally, FFF21 displayed anti-endotoxic effects in vitro. Taken together, our results suggest novel roles for ATIII-derived peptide fragments in host defense.},
  author       = {Papareddy, Praveen and Kalle, Martina and Bhongir, Ravi and Mörgelin, Matthias and Malmsten, Martin and Schmidtchen, Artur},
  issn         = {1083-351X},
  language     = {eng},
  number       = {43},
  pages        = {29790--29800},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Antimicrobial effects of helix D-derived peptides of human antithrombin III.},
  url          = {http://dx.doi.org/10.1074/jbc.M114.570465},
  volume       = {289},
  year         = {2014},
}