Synergistic activity of the plant defensin HsAFP1 and caspofungin against Candida albicans biofilms and planktonic cultures

Vriens, Kim, Cools, Tanne L., Harvey, Peta J., Craik, David J., Spincemaille, Pieter, Cassiman, David, Braem, Annabel, Vleugels, Jozef, Nibbering, Peter H., Drijfhout, Jan Wouter, De Coninck, Barbara, Cammue, Bruno P. A. and Thevissen, Karin (2015) Synergistic activity of the plant defensin HsAFP1 and caspofungin against Candida albicans biofilms and planktonic cultures. PLoS ONE, 10 8: 1-22. doi:10.1371/journal.pone.0132701

Author Vriens, Kim
Cools, Tanne L.
Harvey, Peta J.
Craik, David J.
Spincemaille, Pieter
Cassiman, David
Braem, Annabel
Vleugels, Jozef
Nibbering, Peter H.
Drijfhout, Jan Wouter
De Coninck, Barbara
Cammue, Bruno P. A.
Thevissen, Karin
Title Synergistic activity of the plant defensin HsAFP1 and caspofungin against Candida albicans biofilms and planktonic cultures
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-08-06
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.pone.0132701
Open Access Status DOI
Volume 10
Issue 8
Start page 1
End page 22
Total pages 22
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Plant defensins are small, cysteine-rich peptides with antifungal activity against a broad range of yeast and fungi. In this study we investigated the antibiofilm activity of a plant defensin from coral bells (Heuchera sanguinea), i.e. HsAFP1. To this end, HsAFP1 was heterologously produced using Pichia pastoris as a host. The recombinant peptide rHsAFP1 showed a similar antifungal activity against the plant pathogen Fusarium culmorum as native HsAFP1 purified from seeds. NMR analysis revealed that rHsAFP1 consists of an α-helix and a triple-stranded antiparallel β-sheet stabilised by four intramolecular disulfide bonds. We found that rHsAFP1 can inhibit growth of the human pathogen Candida albicans as well as prevent C. albicans biofilm formation with a BIC50 (i.e. the minimum rHsAFP1 concentration required to inhibit biofilm formation by 50% as compared to control treatment) of 11.00 ± 1.70 μM. As such, this is the first report of a plant defensin exhibiting inhibitory activity against fungal biofilms. We further analysed the potential of rHsAFP1 to increase the activity of the conventional antimycotics caspofungin and amphotericin B towards C. albicans. Synergistic effects were observed between rHsAFP1 and these compounds against both planktonic C. albicans cells and biofilms. Most notably, concentrations of rHsAFP1 as low as 0.53 μM resulted in a synergistic activity with caspofungin against pre-grown C. albicans biofilms. rHsAFP1 was found non-toxic towards human HepG2 cells up to 40 μM, thereby supporting the lack of a general cytotoxic activity as previously reported for HsAFP1. A structure-function study with 24-mer synthetic peptides spanning the entire HsAFP1 sequence revealed the importance of the γ-core and its adjacent regions for HsAFP1 antibiofilm activity. These findings point towards broad applications of rHsAFP1 and its derivatives in the field of antifungal and antibiofilm drug development.
Keyword Plant defensins
Synergistic activity
Candida albicans
Fusarium culmorum
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID G0D5113N
SBO 120005
App 1026501
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
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Created: Fri, 07 Aug 2015, 23:35:18 EST by Susan Allen on behalf of Institute for Molecular Bioscience