Stehr F, Felk A, Kretschmar M, Schaller M, Schäfer W, Hube B
Institut fur Allgemeine Botanik, AMP III, Universität Hamburg.
Mycoses. 2000;43 Suppl 2:17-21.
Candida albicans cannot only infect skin and mucosa, but can also cause life threatening systemic candidosis. While natural barriers and the immune system of healthy individuals normally prevent such infections, virulence factors exist that enable C. albicans to survive on surfaces and the permit the fungus to invade tissues and organs in immunocompromised patients. Adhesions factors, morphological flexibility and hydrolytic enzymes belong to this group of virulence factors.C.albicans appears to be able to use these specific virulence attributes at distinct stages of an infection or in different types of candidosis. For example, distinct adhension factors are important for the persistence of C. albicans on mucosal epithelial cells, while other factors are necessary for the adhesion to endothelial tissue. The differential expression of specific virulence factors at different stages of an infection could be the reason why C. albicans not only has single genes for extracellular hydrolytic enzymes, but gene families. Both secreted aspartate proteinases (Saps) and secreted lipases (Lips) from C. albicans are encoded by at least 10 different genes. This high number of similar genes might empower C. albicans with the ability to secrete a specific and appropriate enzymatic response at distinct stages of an infection. For both gene families differential expression has been shown in vitro and in vivo, which would be reasonable for such an adaptation. Expression studies revealed that distinct SAP and LIP genes were expressed under conditions when potential subtrates ( proteins or lipids) were not present in the growth medium. Such expression patterns would imply that these genes may have functions other than simply providing nutrients for the fungus. The specific transcription of single SAP genes during the course of an infection suggests that these genes may have specific functions during different stages of an infection. In fact, inhibition studies and the use of mutants with targeted gene disruptions showed that distinct SAP genes (SAP1-3) are important durning infections of skin and mucosa, while others (SAP4-6) are most relevant for systemic infections.
白色念珠菌不仅能感染皮肤和黏膜,还会引发危及生命的系统性念珠菌病。虽然健康个体的天然屏障和免疫系统通常能预防此类感染,但白色念珠菌存在毒力因子,使其能够在体表存活,并能侵入免疫功能低下患者的组织和器官。黏附因子、形态可塑性和水解酶都属于这类毒力因子。白色念珠菌似乎能够在感染的不同阶段或不同类型的念珠菌病中利用这些特定的毒力特性。例如,不同的黏附因子对于白色念珠菌在黏膜上皮细胞上的持续存在很重要,而其他因子对于黏附到内皮组织是必需的。在感染的不同阶段特定毒力因子的差异表达可能是白色念珠菌不仅有细胞外水解酶的单个基因,还有基因家族的原因。白色念珠菌分泌的天冬氨酸蛋白酶(Saps)和分泌型脂肪酶(Lips)均由至少10个不同的基因编码。如此大量的相似基因可能使白色念珠菌有能力在感染的不同阶段分泌特定且合适的酶反应。对于这两个基因家族,体外和体内研究均已表明存在差异表达,这种适应性是合理的。表达研究表明,在生长培养基中不存在潜在底物(蛋白质或脂质)的条件下,不同的SAP和LIP基因会表达。这种表达模式意味着这些基因可能具有除了简单为真菌提供营养之外的其他功能。在感染过程中单个SAP基因的特异性转录表明这些基因在感染的不同阶段可能具有特定功能。事实上,抑制研究以及使用靶向基因破坏的突变体表明,不同的SAP基因(SAP1 - 3)在皮肤和黏膜感染期间很重要,而其他基因(SAP4 - 6)与系统性感染最为相关。