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Distinct antifungal mechanisms: beta-defensins require Candida albicans Ssa1 protein, while Trk1p mediates activity of cysteine-free cationic pepti... - PubMed - NCBI
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Antimicrob Agents Chemother. 2006 Jan;50(1):324-31.

Distinct antifungal mechanisms: beta-defensins require Candida albicans Ssa1 protein, while Trk1p mediates activity of cysteine-free cationic peptides.

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1
Department of Oral Biology, School of Dental Medicine, 310 Foster Hall, State University of New York at Buffalo, Main Street Campus, 3435 Main Street, Buffalo, New York 14214, USA.

Abstract

Salivary histatin 5 (Hst 5) kills the fungal pathogen Candida albicans via a multistep process which includes binding to Ssa1/2 proteins on the cell surface and requires the TRK1 potassium transporter. Hst 5-induced membrane permeability to propidium iodide (PI) was nearly abolished in strain CaTK1 (TRK1/trk1), suggesting that Hst 5-induced influx of PI is via Trk1p. To explore the functional role of Trk1p in the mechanism of other antifungal peptides, we evaluated candidacidal activity and PI uptake in wild-type strain CaTK2 (TRK1/TRK1) and strain CaTK1 following treatment with lactoferricin 11 (LFcn 11), bactenecin 16 (BN 16), and virion-associated protein VPR 12. Strain CaTK1 was resistant to killing with these peptides (VPR 12 > LFcn 11 > BN 16), showing the requirement of Trk1p for fungicidal activity. In contrast, human neutrophil defensin 1 (HNP-1), human beta-defensin 2 (hBD-2), and hBD-3 effects on viability of and membrane permeability to PI were not different between mutant and wild-type strains, clearly showing that their candidacidal mechanism does not involve Trk1p as a functional effector. To test whether defensins require binding to Candida surface Ssa1/2 proteins for their activity, we measured the killing effectiveness in SSA1/2 mutant strains. Both hBD-2 and hBD-3, but not HNP-1, exhibited reduced killing of ssa1Delta and ssa2Delta strains compared to the wild type, showing that Ssa1 and Ssa2 proteins are required for their fungicidal activity. These results demonstrate that (i) Trk1p mediates candidacidal activities of cysteine-free peptides, but not of defensins, and (ii) hBD-2 and hBD-3, but not HNP-1, require Ssa1/2p for antifungal activity.

PMID:
16377704
PMCID:
PMC1346820
DOI:
10.1128/AAC.50.1.324-331.2006
[Indexed for MEDLINE]
Free PMC Article
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