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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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The human cathelicidin peptide LL-37 and truncated variants induce segregation of lipids and proteins in the plasma membrane of Candida albicans

Alice L. den Hertog
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands and Present address: VUmc, Department of Molecular Cell Biology and Immunology, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Jan van Marle
  • Department of Cell Biology and Histology/CMO, Academic Medical Center, University of Amsterdam, Meibergdreef 1, NL-1100 DD Amsterdam, The Netherlands
/ Enno C.I. Veerman
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Marianne Valentijn-Benz
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Kamran Nazmi
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Hakan Kalay
  • Department of Molecular Cell Biology and Immunology, VUmc, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Christian H. Grün
  • Department of Molecular Cell Biology and Immunology, VUmc, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Wim van't Hof
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Jan G.M. Bolscher
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
/ Arie V. Nieuw Amerongen
  • Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands
Published Online: 2006-11-02 | DOI: https://doi.org/10.1515/BC.2006.187

Abstract

The human cathelicidin peptide LL-37 and several truncated variants differ in their capability to transmigrate over the plasma membrane of Candida albicans. We investigated whether retention at the cell perimeter or membrane transmigration affects their membrane-disrupting activities and candidacidal properties. Using fluorescein-labeled peptides, we demonstrate that LL-37 and its C-terminally truncated peptide LL-31 remain permanently associated with the perimeter of the cell. The N-terminally truncated peptide RK-31 initially accumulated at the cell boundary, but transmigrated into the cytoplasm within 30 min. The C-terminally truncated peptide LL-25 transmigrated instantaneously into the cytoplasm. The ultrastructural effects on the plasma membrane were studied by freeze-fracture electron microscopy combined with filipin cytochemistry. All peptides, whether they transmigrated over the plasma membrane or not, induced phase separation in the plasma membrane. All peptides induced leakage of cell components, including nucleotides and proteins. Proteins were identified by SDS-PAGE in combination with mass spectrometry, which revealed that predominantly proteins smaller than 50 kDa had leaked out of C. albicans.

Keywords: antimicrobial peptides; Candida albicans; freeze-fracture; LL-37; phase separation

About the article

Corresponding author


Received: April 21, 2006

Accepted: June 8, 2006

Published Online: 2006-11-02

Published in Print: 2006-10-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.187.

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