Extracellular hydrolytic enzymes and their relevance during Candida albicans infections

Candida albicans cannot only infect skin and mucosa,but can also cause life threatening systemic candidosis. While natural barriers and the immune sys tem of healthy individuals normally prevent such infections, virulence fact ors exist that enable C. albicans to survive on surfaces and permit the fun gus to invade tissue and organs in immunocompromised patients. Adhesion fac tors, 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 ty pes of candidosis. For example, distinct adhesion factors are important for the persistence of C. albicans on mucosal epithelial cells, while other fa ctors are necessary for the adhesion to endothelial tissue. This differenti al expression of specific virulence factors at different stages of an infec tion could be the reason why C. albicans not only has single genes for extr acellular 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 o f similar genes might empower C. albicans with the ability to secrete a spe cific and appropriate enzymatic response at distinct stages of an infection . For both gene families differential expression has been shown in vitro an d in vivo, which would be reasonable for such an adaptation. Expression stu dies revealed that distinct SAP and LIP genes were expressed under conditio ns when potential substrates (proteins or lipids) were not present in the g rowth medium. Such expression patterns would imply that these genes may hav e functions other than simply providing nutrients for the fungus. The speci fic transcription of single SAP genes during the course of an infection sug gests that these genes may have specific functions during different stages of an infection. In fact, inhibition studies and the use of mutants with ta rgeted gene disruptions showed that distinct SAP genes (SAP1-3) are importa nt during infections of skin and mucosa, while others (SAP4-6) are more rel evant for systemic infections.