Midkine and pleiotrophin have bactericidal properties - preserved antibacterial activity in a family of heparin-binding growth factors during evolution.
Nordin, Sara LU ; Pasupuleti, Mukesh LU ; Walse, Bjorn ; Malmsten, Martin LU ; Mörgelin, Matthias LU ; Sjogren, Camilla ; Olin, Anders LU ; Collin, Mattias LU
; Schmidtchen, Artur
LU
and Palmer, Ruth
, et al.
(2010)
In Journal of Biological Chemistry
285(21).
p.16105-16115
- Abstract
- Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are upregulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their... (More)
- Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are upregulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three anti-parallel beta-sheets. The antibacterial activity was mapped to the unordered COOH-terminal tails of both molecules and the last beta-sheets of the NH2-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1581767
- author
- Nordin, Sara
LU
; Pasupuleti, Mukesh
LU
; Walse, Bjorn
; Malmsten, Martin
LU
; Mörgelin, Matthias
LU
; Sjogren, Camilla
; Olin, Anders
LU
; Collin, Mattias
LU
; Schmidtchen, Artur
LU
and Palmer, Ruth
, et al. (More)
- Nordin, Sara
LU
; Pasupuleti, Mukesh
LU
; Walse, Bjorn
; Malmsten, Martin
LU
; Mörgelin, Matthias
LU
; Sjogren, Camilla
; Olin, Anders
LU
; Collin, Mattias
LU
; Schmidtchen, Artur
LU
; Palmer, Ruth
and Egesten, Arne
LU
(Less)
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 285
- issue
- 21
- pages
- 16105 - 16115
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000277715900048
- pmid:20308059
- scopus:77952334174
- pmid:20308059
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M109.081232
- language
- English
- LU publication?
- yes
- id
- 161cd507-fb6e-4ab1-970f-ee4e8613125b (old id 1581767)
- alternative location
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871479/
- date added to LUP
- 2016-04-01 10:38:33
- date last changed
- 2022-01-26 01:07:44
@article{161cd507-fb6e-4ab1-970f-ee4e8613125b,
abstract = {{Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are upregulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three anti-parallel beta-sheets. The antibacterial activity was mapped to the unordered COOH-terminal tails of both molecules and the last beta-sheets of the NH2-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics.}},
author = {{Nordin, Sara and Pasupuleti, Mukesh and Walse, Bjorn and Malmsten, Martin and Mörgelin, Matthias and Sjogren, Camilla and Olin, Anders and Collin, Mattias and Schmidtchen, Artur and Palmer, Ruth and Egesten, Arne}},
issn = {{1083-351X}},
language = {{eng}},
number = {{21}},
pages = {{16105--16115}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Midkine and pleiotrophin have bactericidal properties - preserved antibacterial activity in a family of heparin-binding growth factors during evolution.}},
url = {{http://dx.doi.org/10.1074/jbc.M109.081232}},
doi = {{10.1074/jbc.M109.081232}},
volume = {{285}},
year = {{2010}},
}