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Antifungal activities of peptides derived from domain 5 of high-molecular-weight kininogen.

Sonesson, Andreas LU ; Nordahl, Emma LU ; Malmsten, Martin and Schmidtchen, Artur LU (2011) In International Journal of Peptides 2011(Sep 14).
Abstract
In both immunocompromised and immunocompetent patients, Candida and Malassezia are causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind to Candida and other pathogens, leading to activation of the contact system. A cutaneous Candida infection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that... (More)
In both immunocompromised and immunocompetent patients, Candida and Malassezia are causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind to Candida and other pathogens, leading to activation of the contact system. A cutaneous Candida infection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that antifungal peptide fragments are generated through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK, D5-derived peptides, as well as hydrophobically modified D5-derived peptides efficiently killed Candida and Malassezia. Furthermore, the antifungal activity of modified peptides was studied at physiological conditions. Binding of a D5-derived peptide, HKH20 (His(479)-His(498)), to the fungal cell membrane was visualized by fluorescence microscopy. Our data disclose a novel antifungal activity of D5-derived peptides and also show that proteolytic cleavage of HMWK results in fragments exerting antifungal activity. Of therapeutic interest is that structurally modified peptides show an enhanced antifungal activity. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
International Journal of Peptides
volume
2011
issue
Sep 14
publisher
Hindawi Publishing Corporation
external identifiers
  • pmid:21941573
  • scopus:84875802369
ISSN
1687-9775
DOI
10.1155/2011/761037
language
English
LU publication?
yes
id
fae5deaa-eaff-44d2-b4de-eff390f3555c (old id 2168637)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21941573?dopt=Abstract
date added to LUP
2011-10-03 13:13:43
date last changed
2017-08-20 04:35:41
@article{fae5deaa-eaff-44d2-b4de-eff390f3555c,
  abstract     = {In both immunocompromised and immunocompetent patients, Candida and Malassezia are causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind to Candida and other pathogens, leading to activation of the contact system. A cutaneous Candida infection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that antifungal peptide fragments are generated through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK, D5-derived peptides, as well as hydrophobically modified D5-derived peptides efficiently killed Candida and Malassezia. Furthermore, the antifungal activity of modified peptides was studied at physiological conditions. Binding of a D5-derived peptide, HKH20 (His(479)-His(498)), to the fungal cell membrane was visualized by fluorescence microscopy. Our data disclose a novel antifungal activity of D5-derived peptides and also show that proteolytic cleavage of HMWK results in fragments exerting antifungal activity. Of therapeutic interest is that structurally modified peptides show an enhanced antifungal activity.},
  articleno    = {761037},
  author       = {Sonesson, Andreas and Nordahl, Emma and Malmsten, Martin and Schmidtchen, Artur},
  issn         = {1687-9775},
  language     = {eng},
  number       = {Sep 14},
  publisher    = {Hindawi Publishing Corporation},
  series       = {International Journal of Peptides},
  title        = {Antifungal activities of peptides derived from domain 5 of high-molecular-weight kininogen.},
  url          = {http://dx.doi.org/10.1155/2011/761037},
  volume       = {2011},
  year         = {2011},
}