Three anti-microbial peptides were compared with respect to their killing activity against Candida albicans and their ability to disturb its cellular and internal membranes. Histatin 5 is an anti-fungal peptide occurring naturally in human saliva, while dhvar4 and dhvar5 are variants of its active domain, with increased anti-microbial activity. dhvar4has increased amphipathicity compared with histatin 5, whereas dhvar5has amphipathicity comparable with that of histatin 5. All three peptides caused depolarization of the cytoplasmic and/or mitochondrial membrane, indicating membranolytic activity. For the variant peptides both depolarization and killing occurred at a faster rate. With FITC-labelled peptides, no association with the cytoplasmic membrane was observed, contradicting the formation of permanent transmembrane multimeric peptide pores. Instead, the peptides were internalized and act on internal membranes, as demonstrated with mitochondrion- and vacuole-specific markers. In comparison with histatin 5, the variant peptides showed a more destructive effect on mitochondria. Entry of the peptides and subsequent killing were dependent on the metabolic state of the cells. Blocking of the mitochondrial activity led to complete protection against histatin 5 activity, whereas that of dhvar4 was hardly affected and that of dhvar5 was affected only intermediately.
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June 2001
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Research Article|
May 24 2001
Effects of histatin 5 and derived peptides on Candida albicans
Anita L. A. RUISSEN;
Anita L. A. RUISSEN
1
∗Academic Centre for Dentistry Amsterdam (ACTA), Department of Dental Basic Sciences, Section of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
1To whom correspondence should be addressed (e-mail ala.ruissen.obc.acta@med.vu.nl).
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Jasper GROENINK;
Jasper GROENINK
∗Academic Centre for Dentistry Amsterdam (ACTA), Department of Dental Basic Sciences, Section of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Eva J. HELMERHORST;
Eva J. HELMERHORST
†Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118-2392, U.S.A.
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Els WALGREEN-WETERINGS;
Els WALGREEN-WETERINGS
∗Academic Centre for Dentistry Amsterdam (ACTA), Department of Dental Basic Sciences, Section of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Wim van't HOF;
Wim van't HOF
∗Academic Centre for Dentistry Amsterdam (ACTA), Department of Dental Basic Sciences, Section of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Enno C. I. VEERMAN;
Enno C. I. VEERMAN
∗Academic Centre for Dentistry Amsterdam (ACTA), Department of Dental Basic Sciences, Section of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Arie V. NIEUW AMERONGEN
Arie V. NIEUW AMERONGEN
∗Academic Centre for Dentistry Amsterdam (ACTA), Department of Dental Basic Sciences, Section of Oral Biochemistry, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Publisher: Portland Press Ltd
Received:
October 30 2000
Revision Received:
February 22 2001
Accepted:
March 19 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 356 (2): 361–368.
Article history
Received:
October 30 2000
Revision Received:
February 22 2001
Accepted:
March 19 2001
Citation
Anita L. A. RUISSEN, Jasper GROENINK, Eva J. HELMERHORST, Els WALGREEN-WETERINGS, Wim van't HOF, Enno C. I. VEERMAN, Arie V. NIEUW AMERONGEN; Effects of histatin 5 and derived peptides on Candida albicans. Biochem J 1 June 2001; 356 (2): 361–368. doi: https://doi.org/10.1042/bj3560361
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