Midkine and pleiotrophin have bactericidal properties - preserved antibacterial activity in a family of heparin-binding growth factors during evolution.

Research output: Contribution to journalArticle

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.

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Subject classification (UKÄ) – MANDATORY

  • Respiratory Medicine and Allergy
  • Dermatology and Venereal Diseases
  • Infectious Medicine
Original languageEnglish
Pages (from-to)16105-16115
JournalJournal of Biological Chemistry
Volume285
Issue number21
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes

Related research output

Nordin, S., 2013, Respiratory Medicine and Allergology, Lund University. 71 p.

Research output: ThesisDoctoral Thesis (compilation)

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