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Antimicrob. Agents Chemother. doi:10.1128/AAC.01199-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Histatin 5 (P-113) requires a specific peptide sequence for intracellular translocation in Candida albicans and is independent from cell wall binding

Department of Oral Biology and Restorative Dentistry, School of Dental Medicine; State University of New York at Buffalo, Buffalo, New York 14214, USA

^* To whom correspondence should be addressed. Email: edgerto{at}buffalo.edu.

	Abstract

Antifungal activity of histatin 5 (Hst 5) against Candida albicans is initiated through cell wall binding followed by translocation and intracellular targeting. C. albicans cell wall Ssa2 protein is involved in transport of Hst 5 into cells as part of cell killing. P-113, a 12 amino acid candidacidal active fragment of Hst 5, and P-113Q2.10 (inactivated by glutamine substitution for Lys₂ and Lys₁₀) were compared for levels of cell wall binding and intracellular translocation in Candida wt and ssa2 strains. Both P-113 and P-113Q2.10 bound to the cell wall of C. albicans wt and ssa2 cells, although the quantity of P-113Q2.10 in cell wall extracts was higher than that of P-113 in both strains. Increasing the extracellular salt concentration to 100 mM NaCl completely inhibited cell wall association of both peptides, suggesting that these interactions are primarily ionic. Accumulation of P-113 in the cytosol of wt cells reached maximal levels within 15 min (0.26 µg/10⁷ cells), while ssa2 mutant cells had maximal cytosolic levels of less than 0.2 µg/10⁷ cells even after 30 min incubation. Furthermore, P-113 but not P-113Q2.10 showed specific binding with a peptide array of C. albicans Ssa2p. P-113Q2.10 was not transported into the cytosol of either C. albicans wt or ssa2 cells despite high levels of cell wall binding, showing that two cationic lysine residues at position 2 and 10 in P-113 peptide are important for transport into cytosol, and that binding and transport are independent functional events.

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