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ANTIMICROBIAL ACTIVITIES OF HISTIDINE-RICH GLYCOPROTEIN AND CATIONIC PEPTIDES

Rydengård, Victoria LU (2007) In 2007:68
Abstract
In an environment full of potential pathogens it is of importance for organisms to mount a fast and effective defence. Antimicrobial peptides are ancient and integral effector molecules of the innate immune system. They are found in all kinds of species from bacteria to plants and animals, indicating their importance during evolution. They possess a broad-spectrum antimicrobial activity and some peptides can also participate in wound healing and connect the innate and adaptive immune systems.



Results presented in this thesis show that structural motifs connected with heparin-binding may confer antimicrobial activity to a given peptide. Peptides from various heparin-binding endogenous proteins exerted antimicrobial... (More)
In an environment full of potential pathogens it is of importance for organisms to mount a fast and effective defence. Antimicrobial peptides are ancient and integral effector molecules of the innate immune system. They are found in all kinds of species from bacteria to plants and animals, indicating their importance during evolution. They possess a broad-spectrum antimicrobial activity and some peptides can also participate in wound healing and connect the innate and adaptive immune systems.



Results presented in this thesis show that structural motifs connected with heparin-binding may confer antimicrobial activity to a given peptide. Peptides from various heparin-binding endogenous proteins exerted antimicrobial activity against Gram-positive and Gram-negative bacteria and similar results were obtained with consensus sequences for heparin-binding. Furthermore, we demonstrated that replacement of lysine and arginine by histidine in the consensus motifs abrogated the antibacterial effects of these peptides. Antibacterial effects of the histidine-rich consensus peptides were restored by the addition of Zn2+ or low pH. Similar results were obtained with histidine-rich peptides derived from domain 5 of kininogen and histidine-rich glycoprotein (HRGP).



HRGP, an abundant heparin-binding plasma protein, exerted antimicrobial effects against Gram-positive and Gram-negative bacteria and fungi. The antibacterial activity of HRGP was dependent on Zn2+-ions or low pH, and the antifungal activity was increased under low pH conditions.



Electron microscopy demonstrated that HRGP induced lysis of bacteria and fungi. Truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antimicrobial. In addition, HRGP was found to have antifungal effects ex vivo when bound to fibrin clots. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • docent Agerberth, Birgitta, Inst. för medicinsk biokemi och biofysik, Avdelningen för kemi, Karolinska Institutet
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Dermatologi, venereologi, venereology, Dermatology, histidine-rich glycoprotein, heparin-binding, zinc, low pH, Medicine (human and vertebrates), Medicin (människa och djur), innate immunity, antimicrobial
in
2007:68
pages
133 pages
publisher
Institutionen för kliniska vetenskaper, Lunds universitet
defense location
GK-salen, Biomedicinskt centrum, Sölvegatan 19
defense date
2007-05-11 09:00
ISSN
1652-8220
ISBN
978-91-85559-46-6
language
English
LU publication?
yes
id
05dcb27c-a583-47f2-92ad-109491f12cb8 (old id 548526)
date added to LUP
2007-09-12 09:46:46
date last changed
2016-09-19 08:44:52
@phdthesis{05dcb27c-a583-47f2-92ad-109491f12cb8,
  abstract     = {In an environment full of potential pathogens it is of importance for organisms to mount a fast and effective defence. Antimicrobial peptides are ancient and integral effector molecules of the innate immune system. They are found in all kinds of species from bacteria to plants and animals, indicating their importance during evolution. They possess a broad-spectrum antimicrobial activity and some peptides can also participate in wound healing and connect the innate and adaptive immune systems.<br/><br>
<br/><br>
Results presented in this thesis show that structural motifs connected with heparin-binding may confer antimicrobial activity to a given peptide. Peptides from various heparin-binding endogenous proteins exerted antimicrobial activity against Gram-positive and Gram-negative bacteria and similar results were obtained with consensus sequences for heparin-binding. Furthermore, we demonstrated that replacement of lysine and arginine by histidine in the consensus motifs abrogated the antibacterial effects of these peptides. Antibacterial effects of the histidine-rich consensus peptides were restored by the addition of Zn2+ or low pH. Similar results were obtained with histidine-rich peptides derived from domain 5 of kininogen and histidine-rich glycoprotein (HRGP).<br/><br>
<br/><br>
HRGP, an abundant heparin-binding plasma protein, exerted antimicrobial effects against Gram-positive and Gram-negative bacteria and fungi. The antibacterial activity of HRGP was dependent on Zn2+-ions or low pH, and the antifungal activity was increased under low pH conditions.<br/><br>
<br/><br>
Electron microscopy demonstrated that HRGP induced lysis of bacteria and fungi. Truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antimicrobial. In addition, HRGP was found to have antifungal effects ex vivo when bound to fibrin clots.},
  author       = {Rydengård, Victoria},
  isbn         = {978-91-85559-46-6},
  issn         = {1652-8220},
  keyword      = {Dermatologi,venereologi,venereology,Dermatology,histidine-rich glycoprotein,heparin-binding,zinc,low pH,Medicine (human and vertebrates),Medicin (människa och djur),innate immunity,antimicrobial},
  language     = {eng},
  pages        = {133},
  publisher    = {Institutionen för kliniska vetenskaper, Lunds universitet},
  school       = {Lund University},
  series       = {2007:68},
  title        = {ANTIMICROBIAL ACTIVITIES OF HISTIDINE-RICH GLYCOPROTEIN AND CATIONIC PEPTIDES},
  year         = {2007},
}