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Antimicrobial activity of histidine-rich peptides is dependent on acidic conditions.

Kacprzyk, Lukasz; Rydengård, Victoria LU ; Mörgelin, Matthias LU ; Davoudi, Mina LU ; Pasupuleti, Mukesh LU ; Malmsten, Martin and Schmidtchen, Artur LU (2007) In Biochimica et Biophysica Acta - Biomembranes 1768(11). p.2667-2680
Abstract
Synthetic peptides composed of multiples of the consensus heparin-binding Cardin and Weintraub sequences AKKARA and ARKKAAKA are antimicrobial. Replacement of lysine and arginine by histidine in these peptides completely abrogates their antimicrobial and heparin-binding activities at neutral pH. However, the antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) as well as the fungus Candida albicans, was restored at acidic conditions (pH 5.5). Fluorescence microscopy and FACS analysis showed that the binding of the histidine-rich peptides to E. coli and Candida was significantly enhanced at pH 5.5. Likewise, fluorescence studies for... (More)
Synthetic peptides composed of multiples of the consensus heparin-binding Cardin and Weintraub sequences AKKARA and ARKKAAKA are antimicrobial. Replacement of lysine and arginine by histidine in these peptides completely abrogates their antimicrobial and heparin-binding activities at neutral pH. However, the antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) as well as the fungus Candida albicans, was restored at acidic conditions (pH 5.5). Fluorescence microscopy and FACS analysis showed that the binding of the histidine-rich peptides to E. coli and Candida was significantly enhanced at pH 5.5. Likewise, fluorescence studies for assessment of membrane permeation as well as electron microscopy analysis of peptide-treated bacteria, paired with studies of peptide effects on liposomes, demonstrated that the peptides induce membrane lysis only at acidic pH. No discernible hemolysis was noted for the histidine-rich peptides. Similar pH-dependent antimicrobial activities were demonstrated for peptides derived from histidine-rich and heparin-binding regions of human kininogen and histidine-rich glycoprotein. The results demonstrate that the presence of an acidic environment is an important regulator of the activity of histidine-rich antimicrobial peptides. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Histidine-rich glycoprotein, Antimicrobial peptide, pH, Heparin-binding
in
Biochimica et Biophysica Acta - Biomembranes
volume
1768
issue
11
pages
2667 - 2680
publisher
Elsevier
external identifiers
  • wos:000251493700003
  • scopus:35848960809
ISSN
0005-2736
DOI
10.1016/j.bbamem.2007.06.020
language
English
LU publication?
yes
id
bffc8428-5eb1-4fce-a63f-c294778d4186 (old id 540475)
date added to LUP
2008-08-21 14:05:52
date last changed
2017-08-06 04:35:20
@article{bffc8428-5eb1-4fce-a63f-c294778d4186,
  abstract     = {Synthetic peptides composed of multiples of the consensus heparin-binding Cardin and Weintraub sequences AKKARA and ARKKAAKA are antimicrobial. Replacement of lysine and arginine by histidine in these peptides completely abrogates their antimicrobial and heparin-binding activities at neutral pH. However, the antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) as well as the fungus Candida albicans, was restored at acidic conditions (pH 5.5). Fluorescence microscopy and FACS analysis showed that the binding of the histidine-rich peptides to E. coli and Candida was significantly enhanced at pH 5.5. Likewise, fluorescence studies for assessment of membrane permeation as well as electron microscopy analysis of peptide-treated bacteria, paired with studies of peptide effects on liposomes, demonstrated that the peptides induce membrane lysis only at acidic pH. No discernible hemolysis was noted for the histidine-rich peptides. Similar pH-dependent antimicrobial activities were demonstrated for peptides derived from histidine-rich and heparin-binding regions of human kininogen and histidine-rich glycoprotein. The results demonstrate that the presence of an acidic environment is an important regulator of the activity of histidine-rich antimicrobial peptides.},
  author       = {Kacprzyk, Lukasz and Rydengård, Victoria and Mörgelin, Matthias and Davoudi, Mina and Pasupuleti, Mukesh and Malmsten, Martin and Schmidtchen, Artur},
  issn         = {0005-2736},
  keyword      = {Histidine-rich glycoprotein,Antimicrobial peptide,pH,Heparin-binding},
  language     = {eng},
  number       = {11},
  pages        = {2667--2680},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Biomembranes},
  title        = {Antimicrobial activity of histidine-rich peptides is dependent on acidic conditions.},
  url          = {http://dx.doi.org/10.1016/j.bbamem.2007.06.020},
  volume       = {1768},
  year         = {2007},
}