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The epithelium-produced growth factor midkine has fungicidal properties.

Nordin, Sara LU ; Sonesson, Andreas LU ; Malmsten, Martin; Mörgelin, Matthias LU and Egesten, Arne LU (2012) In Journal of Antimicrobial Chemotherapy 67(8). p.1927-1936
Abstract
OBJECTIVES: The skin encounters many potential pathogens present in the environment, where Candida spp. are among the most common causes of fungal infestation. Midkine (MK) is a heparin-binding growth factor that is constitutively produced in the epidermis and this study looks at the antifungal activity of MK, potential co-localization and mode of action of MK.



METHODS AND RESULTS: We show that MK is expressed in association with fungal infections of the skin. In vitro, MK showed strong fungicidal activity against Candida albicans and Candida parapsilosis. Scanning electron microscopy of fungi revealed blebbing and leakage of intracellular contents, indicating membrane interactions. Immunoelectron microscopy showed... (More)
OBJECTIVES: The skin encounters many potential pathogens present in the environment, where Candida spp. are among the most common causes of fungal infestation. Midkine (MK) is a heparin-binding growth factor that is constitutively produced in the epidermis and this study looks at the antifungal activity of MK, potential co-localization and mode of action of MK.



METHODS AND RESULTS: We show that MK is expressed in association with fungal infections of the skin. In vitro, MK showed strong fungicidal activity against Candida albicans and Candida parapsilosis. Scanning electron microscopy of fungi revealed blebbing and leakage of intracellular contents, indicating membrane interactions. Immunoelectron microscopy showed accumulation of MK in association with the membrane, but also a high degree of internalization, suggesting intracellular targets as well. Using liposome models mimicking fungal and human cell membranes (i.e. ergosterol- and cholesterol-containing membranes, respectively), MK was found to disrupt ergosterol-containing membranes to a higher degree than cholesterol-containing vesicles. Addition of increasing concentrations of salt caused a partial and dose-dependent decrease in the fungicidal activity exerted by MK in parallel with a decreased affinity for the yeast. However, at salt concentrations similar to those of an epithelial context (i.e. 50-100 mM), MK retained most of its fungicidal activity, in contrast to that of plasma (150 mM).



CONCLUSIONS: The findings suggest that MK plays a role in host defence against fungal infections and could serve as a template for development of novel antifungal treatments. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Antimicrobial Chemotherapy
volume
67
issue
8
pages
1927 - 1936
publisher
Oxford University Press
external identifiers
  • wos:000306366000018
  • pmid:22535623
  • scopus:84864511013
ISSN
1460-2091
DOI
10.1093/jac/dks136
language
English
LU publication?
yes
id
668ecd8a-4c36-4819-848f-ca6280deac9b (old id 2519018)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22535623?dopt=Abstract
date added to LUP
2012-05-07 11:43:52
date last changed
2017-09-17 03:13:50
@article{668ecd8a-4c36-4819-848f-ca6280deac9b,
  abstract     = {OBJECTIVES: The skin encounters many potential pathogens present in the environment, where Candida spp. are among the most common causes of fungal infestation. Midkine (MK) is a heparin-binding growth factor that is constitutively produced in the epidermis and this study looks at the antifungal activity of MK, potential co-localization and mode of action of MK. <br/><br>
<br/><br>
METHODS AND RESULTS: We show that MK is expressed in association with fungal infections of the skin. In vitro, MK showed strong fungicidal activity against Candida albicans and Candida parapsilosis. Scanning electron microscopy of fungi revealed blebbing and leakage of intracellular contents, indicating membrane interactions. Immunoelectron microscopy showed accumulation of MK in association with the membrane, but also a high degree of internalization, suggesting intracellular targets as well. Using liposome models mimicking fungal and human cell membranes (i.e. ergosterol- and cholesterol-containing membranes, respectively), MK was found to disrupt ergosterol-containing membranes to a higher degree than cholesterol-containing vesicles. Addition of increasing concentrations of salt caused a partial and dose-dependent decrease in the fungicidal activity exerted by MK in parallel with a decreased affinity for the yeast. However, at salt concentrations similar to those of an epithelial context (i.e. 50-100 mM), MK retained most of its fungicidal activity, in contrast to that of plasma (150 mM). <br/><br>
<br/><br>
CONCLUSIONS: The findings suggest that MK plays a role in host defence against fungal infections and could serve as a template for development of novel antifungal treatments.},
  author       = {Nordin, Sara and Sonesson, Andreas and Malmsten, Martin and Mörgelin, Matthias and Egesten, Arne},
  issn         = {1460-2091},
  language     = {eng},
  number       = {8},
  pages        = {1927--1936},
  publisher    = {Oxford University Press},
  series       = {Journal of Antimicrobial Chemotherapy},
  title        = {The epithelium-produced growth factor midkine has fungicidal properties.},
  url          = {http://dx.doi.org/10.1093/jac/dks136},
  volume       = {67},
  year         = {2012},
}