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タイトル: | Kinin release from human kininogen by 10 aspartic proteases produced by pathogenic yeast Candida albicans |
著者: | Kozik, Andrzej Gogol, Mariusz Bochenska, Oliwia Karkowska-Kuleta, Justyna Wolak, Natalia Kamysz, Wojciech Aoki, Wataru https://orcid.org/0000-0002-3118-9390 (unconfirmed) Ueda, Mitsuyoshi Faussner, Alexander Rapala-Kozik, Maria |
著者名の別形: | 青木, 航 植田, 充美 |
キーワード: | Candidiasis Human kininogen Met-Lys-bradykinin Des-Arg-kinins Bradykinin B2-subtype receptors Pichia pastoris |
発行日: | 4-Mar-2015 |
出版者: | BioMed Central Ltd. |
誌名: | BMC Microbiology |
巻: | 15 |
論文番号: | 60 |
抄録: | Background: Candida albicans yeast produces 10 distinct secreted aspartic proteases (Saps), which are some of the most important virulence factors of this pathogenic fungus. One of the suggested roles of Saps is their deregulating effect on various proteolytic cascades that constitute the major homeostatic systems in human hosts, including blood coagulation, fibrinolysis, and kallikrein-kinin systems. This study compared the characteristics of the action of all 10 Saps on human kininogens, which results in generating proinflammatory bradykinin-related peptides (kinins). Results: Recombinant forms of Saps, heterologously overexpressed in Pichia pastoris were applied. Except for Sap7 and Sap10, all Saps effectively cleaved the kininogens, with the highest hydrolytic activity toward the low-molecular-mass form (LK). Sap1-6 and 8 produced a biologically active kinin - Met-Lys-bradykinin - and Sap3 was exceptional in terms of the kinin-releasing yield (>60% LK at pH 5.0 after 24 hours). Des-Arg<sup>1</sup>-bradykinin was released from LK by Sap9 at a comparably high yield, but this peptide was assumed to be biologically inactive because it was unable to interact with cellular B2-type kinin receptors. However, the collaborative actions of Sap9 and Sap1, -2, -4-6, and -8 on LK rerouted kininogen cleavage toward the high-yield release of the biologically active Met-Lys-bradykinin. Conclusions: Our present results, together with the available data on the expression of individual SAP genes in candidal infection models, suggest a biological potential of Saps to produce kinins at the infection foci. The kinin release during candidiasis can involve predominant and complementary contributions of two different Sap3- and Sap9-dependent mechanisms. |
著作権等: | © 2015 Kozik et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. |
URI: | http://hdl.handle.net/2433/213938 |
DOI(出版社版): | 10.1186/s12866-015-0394-8 |
PubMed ID: | 25879450 |
出現コレクション: | 学術雑誌掲載論文等 |
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