The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms

Vriens, Kim, Cools, Tanne L., Harvey, Peta J., Craik, David J., Braem, Annabel, Vleugels, Jozef, Coninck, Barbara De, Cammue, Bruno P. A. and Thevissen, Karin (2016) The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms. Peptides, 75 71-79. doi:10.1016/j.peptides.2015.11.001

Author Vriens, Kim
Cools, Tanne L.
Harvey, Peta J.
Craik, David J.
Braem, Annabel
Vleugels, Jozef
Coninck, Barbara De
Cammue, Bruno P. A.
Thevissen, Karin
Title The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms
Journal name Peptides   Check publisher's open access policy
ISSN 1873-5169
Publication date 2016-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.peptides.2015.11.001
Open Access Status Not Open Access
Volume 75
Start page 71
End page 79
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2016
Language eng
Formatted abstract
The radish defensin RsAFP2 was previously characterized as a peptide with potent antifungal activity against several plant pathogenic fungi and human pathogens, including Candida albicans. RsAFP2 induces apoptosis and impairs the yeast-to-hypha transition in C. albicans. As the yeast-to-hypha transition is considered important for progression to mature biofilms, we analyzed the potential antibiofilm activity of recombinant (r)RsAFP2, heterologously expressed in Pichia pastoris, against C. albicans biofilms. We found that rRsAFP2 prevents C. albicans biofilm formation with a BIC-2 (i.e., the minimal rRsAFP2 concentration that inhibits biofilm formation by 50% as compared to control treatment) of 1.65 ± 0.40 mg/mL. Moreover, biofilm-specific synergistic effects were observed between rRsAFP2 doses as low as 2.5 μg/mL to 10 μg/mL and the antimycotics caspofungin and amphotericin B, pointing to the potential of RsAFP2 as a novel antibiofilm compound. In addition, we characterized the solution structure of rRsAFP2 and compared it to that of RsAFP1, another defensin present in radish seeds. These peptides have similar amino acid sequences, except for two amino acids, but rRsAFP2 is more potent than RsAFP1 against planktonic and biofilm cultures. Interestingly, as in case of rRsAFP2, also RsAFP1 acts synergistically with caspofungin against C. albicans biofilms in a comparable low dose range as rRsAFP2. A structural comparison of both defensins via NMR analysis revealed that also rRsAFP2 adopts the typical cysteine-stabilized αβ-motif of plant defensins, however, no structural differences were found between these peptides that might result in their differential antifungal/antibiofilm potency. This further suggests that the conserved structure of RsAFP1 and rRsAFP2 bears the potential to synergize with antimycotics against C. albicans biofilms.
Keyword Candida albicans
Fungal biofilm
NMR analysis
Plant defensin
Recombinant protein production
Q-Index Code C1
Q-Index Status Provisional Code
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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