Thioredoxin-Peroxidase von C. albicans als virulenzspezifischer Marker

Die vorliegende Erfindung betrifft Verfahren zur Charakterisierung und/oder zum Nachweis von Differenzierungsstadien von Candida-Zellen, Verfahren zum Nachweis einer Candida-Infektion in einer biologischen Probe, die Thioredoxin-Peroxidase von Candida, gegen die Thioredoxin-Peroxidase gerichtete Antikoerper, diagnostische und pharmazeutische Zusammensetzungen, die die Thioredoxin-Peroxidase oder dagegen gerichtete Antikoerper enthalten, einen Kit zur Identifizierung der Thioredoxin-Peroxidase, die Verwendung einer die Thioredoxin- Peroxidase codierenden Nucleinsaeure oder der Thioredoxobn-Peroxidase zur Herstellung einer diagnostischen oder pharmazeutischen Zusammensetzung und die Verwendung eines gegen die Thioredoxin-Peroxidase gerichteten Antikoerpers zum Nachweis von Differenzierungsstadien von Candida-Zellen und/oder einer Candida-Infektion sowie zur Herstellung einer diagnostischen oder pharmazeutischen Zusammensetzung.

WO2004101612 A UPAB: 20041216 NOVELTY - Characterizing and/or detecting the differentiation stages of Candida cells (A), is new. DETAILED DESCRIPTION - Method for characterizing and/or detecting the differentiation stages of Candida cells (A) comprises incubating (A), or their fractions, with an agent (I) for identifying a Candida protein (II) that has thioredoxin peroxidase activity, or a fragment of it, then examining the interaction between (I) and (II) to determine the cellular localization of (II). Detecting (II) in the cell wall indicates the virulent hyphal stage, while detecting (II) in the nucleus and/or cytoplasm indicates the avirulent yeast stage. INDEPENDENT CLAIMS are also included for: (1) detecting Candida infection, in a human or animal sample, that uses (I) to detect (II) in the sample and/or in the cell wall of Candida present in the sample; (2) protein (IIa) with thioredoxin peroxidase activity that has a 196 amino acid sequence (1), encoded by a 591 bp nucleic acid sequence (2), both reproduced; (3) antibodies (Ab) that bind specifically to (IIa); (4) antibodies (AAb) that bind specifically to Ab; (5) diagnostic or pharmaceutical composition that contains a nucleic acid encoding a protein, from a pathogenic fungus, with thioredoxin peroxidase activity, or related vectors, host cells, proteins and antibodies; and (6) kit for identifying (II) and/or detecting virulence in C. albicans in vitro, comprising a container of antibodies specific for (II). ACTIVITY - Fungicide. No biological data given. MECHANISM OF ACTION - Inhibition of fungal thioredoxin peroxidase; vaccine; passive immunization. USE - The method is used to detect/differentiate between the virulant hyphal and avirulent yeast forms of Candida. Also nucleic acid that encodes the thioredoxin peroxidase of C. albicans can be used to isolate homologous sequences from other fungi; for preparation of therapeutic or diagnostic compositions; and to screen for agents that inhibit expression or activity of thioredoxin peroxidase in pathogens (potential antifungal agents); and the proteins encoded by them are used similarly, particularly in vaccines, and antibodies against these proteins are useful as reagents in the new process (especially for detection of invasive candidiasis in blood) and for passive immunization (all claimed). ADVANTAGE - The method provides exact and quick diagnosis of Candida infection, and therapeutic agents that target fungal thioredoxin peroxidase should be free of side effects.