Lermann Ulrich, Morschhäuser Joachim
Institut für Molekulare Infektionsbiologie, Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.
Microbiology (Reading). 2008 Nov;154(Pt 11):3281-3295. doi: 10.1099/mic.0.2008/022525-0.
A well-known virulence attribute of the human-pathogenic yeast Candida albicans is the secretion of aspartic proteases (Saps), which may contribute to colonization and infection of different host niches by degrading tissue barriers, destroying host defence molecules, or digesting proteins for nutrient supply. The role of individual Sap isoenzymes, which are encoded by a large gene family, for the pathogenicity of C. albicans has been investigated by assessing the virulence of mutants lacking specific SAP genes and by studying the expression pattern of the SAP genes in various models of superficial and systemic infections. We used a recombination-based genetic reporter system to detect the induction of the SAP1-SAP6 genes during infection of reconstituted human vaginal epithelium. Only SAP5, but none of the other tested SAP genes, was detectably activated in this in vitro infection model. To directly address the importance of the SAP1-SAP6 genes for invasion of reconstituted human epithelia (RHE), we constructed a set of mutants of the wild-type C. albicans model strain SC5314 in which either single or multiple SAP genes were specifically deleted. Even mutants lacking all of the SAP1-SAP3 or the SAP4-SAP6 genes displayed the same capacity to invade and damage both oral and vaginal RHE as their wild-type parental strain, in contrast to a nonfilamentous efg1Delta mutant that was avirulent under these conditions. We therefore conclude from these results that the secreted aspartic proteases Sap1p-Sap6p are not required for invasion of RHE by C. albicans.
人类致病酵母白色念珠菌的一个著名毒力特性是分泌天冬氨酸蛋白酶（Saps），这些酶可能通过降解组织屏障、破坏宿主防御分子或消化蛋白质以提供营养，从而有助于在不同宿主生态位中定殖和感染。由一个大基因家族编码的各个Sap同工酶在白色念珠菌致病性中的作用，已通过评估缺乏特定SAP基因的突变体的毒力以及研究SAP基因在各种浅表和全身感染模型中的表达模式来进行研究。我们使用基于重组的遗传报告系统来检测重组人阴道上皮感染期间SAP1 - SAP6基因的诱导情况。在这个体外感染模型中，仅检测到SAP5被激活，而其他测试的SAP基因均未被激活。为了直接探究SAP1 - SAP6基因对重组人上皮（RHE）侵袭的重要性，我们构建了一组野生型白色念珠菌模型菌株SC5314的突变体，其中单个或多个SAP基因被特异性删除。与在这些条件下无毒性的非丝状efg1Delta突变体相反，即使是缺乏所有SAP1 - SAP3或SAP4 - SAP6基因的突变体，侵袭和损伤口腔及阴道RHE的能力也与它们的野生型亲本菌株相同。因此，我们从这些结果得出结论，白色念珠菌侵袭RHE并不需要分泌的天冬氨酸蛋白酶Sap1p - Sap6p。
