Han Zhiping, Kautto Liisa, Nevalainen Helena
Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia.
Biomolecular Frontiers Research Centre, Macquarie University, Sydney, Australia.
PLoS One. 2017 Jan 6;12(1):e0169403. doi: 10.1371/journal.pone.0169403. eCollection 2017.
Scedosporium aurantiacum is an opportunistic filamentous fungus increasingly isolated from the sputum of cystic fibrosis patients, and is especially prevalent in Australia. At the moment, very little is known about the infection mechanism of this fungus. Secreted proteases have been shown to contribute to fungal virulence in several studies with other fungi. Here we have compared the profiles of proteases secreted by a clinical isolate Scedosporium aurantiacum (WM 06.482) and an environmental strain (WM 10.136) grown on a synthetic cystic fibrosis sputum medium supplemented with casein or mucin. Protease activity was assessed using class-specific substrates and inhibitors. Subtilisin-like and trypsin-like serine protease activity was detected in all cultures. The greatest difference in the secretion of proteases between the two strains occurred in mucin-supplemented medium, where the activities of the elastase-like, trypsin-like and aspartic proteases were, overall, 2.5-75 fold higher in the clinical strain compared to the environmental strain. Proteases secreted by the two strains in the mucin-supplemented medium were further analyzed by mass spectrometry. Six homologs of fungal proteases were identified from the clinical strain and five from the environmental strain. Of these, three were common for both strains including a subtilisin peptidase, a putative leucine aminopeptidase and a PA-SaNapH-like protease. Trypsin-like protease was identified by mass spectrometry only in the clinical isolate even though trypsin-like activity was present in all cultures. In contrast, high elastase-like activity was measured in the culture supernatant of the clinical strain but could not be identified by mass spectrometry searching against other fungi in the NCBI database. Future availability of an annotated genome will help finalise identification of the S. aurantiacum proteases.
橙色拟青霉是一种机会性丝状真菌,越来越多地从囊性纤维化患者的痰液中分离出来,在澳大利亚尤为普遍。目前,对这种真菌的感染机制知之甚少。在其他真菌的多项研究中,已表明分泌的蛋白酶有助于真菌的毒力。在这里,我们比较了在添加酪蛋白或粘蛋白的合成囊性纤维化痰液培养基上生长的临床分离株橙色拟青霉(WM 06.482)和环境菌株(WM 10.136)分泌的蛋白酶谱。使用类特异性底物和抑制剂评估蛋白酶活性。在所有培养物中均检测到枯草杆菌蛋白酶样和胰蛋白酶样丝氨酸蛋白酶活性。两种菌株之间蛋白酶分泌的最大差异出现在添加粘蛋白的培养基中,与环境菌株相比,临床菌株中弹性蛋白酶样、胰蛋白酶样和天冬氨酸蛋白酶的活性总体上高2.5至75倍。通过质谱进一步分析了两种菌株在添加粘蛋白的培养基中分泌的蛋白酶。从临床菌株中鉴定出6种真菌蛋白酶同源物,从环境菌株中鉴定出5种。其中,三种是两种菌株共有的,包括一种枯草杆菌蛋白酶、一种假定的亮氨酸氨肽酶和一种PA-SaNapH样蛋白酶。尽管所有培养物中都存在胰蛋白酶样活性,但仅在临床分离株中通过质谱鉴定出胰蛋白酶样蛋白酶。相比之下,在临床菌株的培养上清液中检测到高弹性蛋白酶样活性,但通过在NCBI数据库中针对其他真菌进行质谱搜索无法鉴定。未来注释基因组的可用性将有助于最终确定橙色拟青霉蛋白酶的鉴定。