Effects of histatin 5 and derived peptides on Candida albicans

被引:85
作者
Ruissen, ALA
Groenink, J
Helmerhorst, EJ
Walgreen-Weterings, E
van't Hof, W
Veerman, ECI
Amerongen, AVN
机构
[1] Acad Ctr Dent Amsterdam, Dept Dent Basic Sci, Sect Oral Biochem, NL-1081 BT Amsterdam, Netherlands
[2] Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA
关键词
anti-microbial; dhvar peptides; mitochondria; respiration; vacuoles;
D O I
10.1042/0264-6021:3560361
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. dhvar4 has increased amphipathicity compared with histatin 5, whereas dhvar5 has 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.
引用
收藏
页码:361 / 368
页数:8
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