Genetically engineered human salivary histatin genes are functional in Candida albicans: development of a new system for studying histatin candidacidal activity.
Histatins are a structurally related family of salivary proteins known as histidine-rich proteins that are produced and secreted by the human major salivary glands. In vitro, histatins are potent cytotoxic proteins with selectivity for pathogenic yeasts including Candida albicans. Studies that investigate the mechanism of action of histatin proteins upon this important human pathogen have used a candidacidal assay in which the histatin is applied extracellularly. In order to develop a model system to study the mechanism of histatin action independently from binding and translocation events, the authors constructed C. albicans strains that contain chromosomally encoded human salivary histatin genes under the control of a regulated promoter. Intracellular expression of either histatin 5 or histatin 3 induced cell killing and ATP release in parallel. Since histatin killing can be initiated solely from intracellular sites, extracellular binding and internalization are preceding transport events. Thus the mechanism of histatin-induced ATP release does not require extracellular binding, and intracellular targets alone can activate ATP release. By employing a codon-optimization strategy it was shown that expression of heterologous sequences in C. albicans can be a useful tool for functional studies.
Baev
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Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo Main Street Campus, 3435 Main Street, Buffalo, NY 14214, USA.
Li
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Edgerton
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D054808:Histatins; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000494:pharmacology*; D000099053:Histidine-Rich Glycoprotein
D000935:Antifungal Agents; C068075:HTN3 protein, human; D054808:Histatins; D011506:Proteins; C018149:STATH protein, human; D012471:Salivary Proteins and Peptides; D000099053:Histidine-Rich Glycoprotein; D000255:Adenosine Triphosphate