ANTIMICROBIAL ACTIVITIES OF HISTIDINE-RICH GLYCOPROTEIN AND CATIONIC PEPTIDES
(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:
https://lup.lub.lu.se/record/548526
- author
- Rydengård, Victoria LU
- supervisor
- opponent
-
- docent Agerberth, Birgitta, Inst. för medicinsk biokemi och biofysik, Avdelningen för kemi, Karolinska Institutet
- organization
- publishing date
- 2007
- 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 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-85559-46-6
- language
- English
- LU publication?
- yes
- additional info
- E Andersson, V Rydengård, A Sonesson, M Mörgelin, L Björck and A Schmidtchen. 2004. Antimicrobial activities of heparin-binding peptides. Eur J Biochem, vol 271 pp 1219-26.V Rydengård, E Andersson Nordahl and A Schmidtchen. 2006. Zinc potentiates the antibacterial effects of histidine-rich peptides against Enterococcus faecalis FEBS J., vol 273 pp 2399-406.L Kacprzyk, V Rydengård, M Malmsten and A Schmidtchen. . Antimicrobial activity of histidine-rich peptides is dependent of acidic conditions (manuscript)V Rydengård, A-K Olsson, M Mörgelin and A Schmidtchen. 2007. Histidine-rich glycoprotein exerts antibacterial activity FEBS J., vol 274 pp 377-89.V Rydengård, L Kacprzyk, A-K Olsson, M Mörgelin, M Malmsten and A Schmidtchen. . Antifungal activity of histidine-rich glycoprotein (manuscript)
- id
- 05dcb27c-a583-47f2-92ad-109491f12cb8 (old id 548526)
- date added to LUP
- 2016-04-01 15:30:49
- date last changed
- 2019-05-21 08:47:02
@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}}, keywords = {{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}}, publisher = {{Institutionen för kliniska vetenskaper, Lunds universitet}}, school = {{Lund University}}, series = {{2007:68}}, title = {{ANTIMICROBIAL ACTIVITIES OF HISTIDINE-RICH GLYCOPROTEIN AND CATIONIC PEPTIDES}}, url = {{https://lup.lub.lu.se/search/files/4409395/548527.pdf}}, year = {{2007}}, }