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Projekt
Role of protein-mannosyl-transferases (PMTs) in virulence of Cryptococcus neoformans
Antragsteller
Dr. Klaus Bruno Lengeler
Fachliche Zuordnung
Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
Förderung
Förderung von 2004 bis 2007
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5426567
O-glycosylation, the addition of carbohydrate residues to proteins is a very important protein modification and is commonly found in all eukaryotic organisms. A wide variety of proteins is affected by O-glycosylation. In fungal organisms mainly secreted proteins and cell-membrane associated proteins are O-glycosylated while in mammals also O-glycosylated cytosolic proteins have been identified. Virulence of the opportunistic fungal pathogen Cryptococcus neoformans is mainly determined by extracellular factors such as a polysaccharide capsule, extracellular enzymes, cell-surface antigens, or melanin, a pigment deposited into the cell-wall of the organism. Therefore, O-glycosylation may have a huge impact on virulence of this organism through effects on biosynthesis, localization and function of these virulence factors. This project aims to analyze the influence of O-glycosylation on these virulence factors by characterizing the protein mannosyltransferase (PMI-) gene family of C. neoformans. This gene family, which consists of three members, PMTI, PMT2, and PMT4, encodes enzymes that catalyze the initial step of protein O-glycosylation, the addition of mannose residues to serine or threonine residues of respective target proteins. Effects of deleting PMT-genes on virulence of C neoformans will be determined by routine in vitro and in vivo assays analyzing specific virulence factors and infectivity of the pathogen, respectively.
DFG-Verfahren
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