title: The action of ten secreted aspartic proteases of pathogenic yeast Candida albicans on major human salivary antimicrobial peptide, histatin 5.
abstract: Candida albicans, belonging to the most common fungal pathogens of humans, exploits many virulence factors to infect the host, of which the most important is a family of ten secreted aspartic proteases (Saps) that cleave numerous peptides and proteins, often deregulating the host's biochemical homeostasis. It was recently shown that C. albicans cells can inactivate histatin5 (His5), a salivary histidine-rich anticandidal peptide, through the hydrolytic action of Saps. However, the current data on this subject are incomplete as only four out of ten Saps have been studied with respect to hydrolytic processing of His5 (Sap2, Sap5, Sap9-10). The aim of the study was to investigate the action of all Saps on His5 and to characterize this process in terms of peptide chemistry. It was shown that His5 was degraded by seven out of ten Saps (Sap1-4, Sap7-9) over a broad range of pH. The cleavage rate decreased in an order of Sap2>Sap9>Sap3>Sap7>Sap4>Sap1>Sap8. The degradation profiles for Sap2 and Sap9 were similar to those previously reported; however, in contrast to the previous study, Sap10 was shown to be unable to cleave His5. On a long-time scale, the peptide was completely degraded and lost its antimicrobial potential but after a short period of Sap treatment several shorter peptides (His1-13, His1-17, His1-21) that still decreased fungal survival were released. The results, presented hereby, provide extended characteristics of the action of C. albicans extracellular proteases on His5. Our study contribute to deepening the knowledge on the interactions between fungal pathogens and the human host.
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Bochenska
authors.affiliation: Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rapala-Kozik
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Wolak
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Aoki
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
mesh_terms: D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology*; D005656:Fungal Proteins / Q000737:chemistry*; D054808:Histatins / Q000737:chemistry* / Q000494:pharmacology; D054884:Host-Pathogen Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D059748:Proteolysis
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; C068075:HTN3 protein, human; D054808:Histatins; D016282:Aspartic Acid Endopeptidases