Bochenska Oliwia, Rapala-Kozik Maria, Wolak Natalia, Aoki Wataru, Ueda Mitsuyoshi, Kozik Andrzej
Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland.
Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland.
Acta Biochim Pol. 2016;63(3):403-10. doi: 10.18388/abp.2016_1318. Epub 2016 Jul 8.
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.
白色念珠菌是人类最常见的真菌病原体之一，它利用多种毒力因子感染宿主，其中最重要的是一组由十种分泌型天冬氨酸蛋白酶（Saps）组成的家族，这些蛋白酶可切割多种肽和蛋白质，常常破坏宿主的生化稳态。最近有研究表明，白色念珠菌细胞可通过Saps的水解作用使富含组氨酸的唾液抗念珠菌肽组蛋白5（His5）失活。然而，目前关于这一主题的数据并不完整，因为在十种Saps中，仅有四种（Sap2、Sap5、Sap9 - 10）针对His5的水解加工进行了研究。本研究的目的是探究所有Saps对His5的作用，并从肽化学角度对这一过程进行表征。结果表明，十种Saps中有七种（Sap1 - 4、Sap7 - 9）在较宽的pH范围内可降解His5。切割速率按以下顺序降低：Sap2 > Sap9 > Sap3 > Sap7 > Sap4 > Sap1 > Sap8。Sap2和Sap9的降解谱与先前报道的相似；然而，与先前的研究不同，Sap10被证明无法切割His5。从长期来看，该肽被完全降解并失去其抗菌潜力，但在经过短时间的Sap处理后，会释放出几种仍能降低真菌存活率的较短肽段（His1 - 13、His1 - 17、His1 - 21）。本文所呈现的结果提供了白色念珠菌细胞外蛋白酶对His5作用的扩展特征。我们的研究有助于加深对真菌病原体与人类宿主之间相互作用的认识。
