[Extracellular hydrolytic enzymes and their relevance during Candida albicans infections]. / Extrazelluläre hydrolytische Enzyme und ihre Relevanz bei Candida-albicans-Infektionen.

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.

Synthesis and inhibition of human leucocyte elastase by functionalized N-aryl azetidin-2-ones: effect of different substituents on the aromatic ring.

N-aryl-3,3-difluoroazetidin-2-ones featured by a latent electrophilic methylene quinoniminium function have been synthesized and evaluated as inhibitors of human leucocyte elastase. To promote hydrophobic interactions with the enzyme, to increase the rates of beta-lactam ring opening and of benzylic group departure, or to induce hydrosolubility, these compounds incorporate on their aromatic ring either an alkyl moiety, a methoxy substituent or a carboxylic group. Some of these beta-lactams proved to be good inactivators of human leucocyte elastase.