Prof. Dr. Francoise Routier
Glycoparasitology
Contact: Prof. Dr. Françoise H. Routier
Routier.Francoise(at)mh-hannover.de
Current group members:
Sebastian Damerow Postdoctoral researcher
Jakob Engel, Ph.D student
Anke Krüger Ph.D student
Patricia Zarnovican, technical assistant
Research Overview:
Pathogens are surrounded either by a cell wall or a dense glycocalix extremely rich in carbohydrates. This cell coat protects the pathogen from its environment and enables interaction with its host. Therefore its integrity is often crucial for the organism survival or for the establishment of infection and many of the medicines currently in use act by interfering with the cell coat assembly.
Our group concentrates on the role of specific carbohydrates in eukaryotic pathogens. The parasites Leishmania, responsible for human diseases collectively called leishmaniases and the opportunistic fungus Aspergillus fumigatus, the agent of invasive aspergillosis (a leading cause of infectious death in modern hospitals) are our model organisms. The existing drugs against these organisms often pose problems of toxicity and the occurrence of therapeutic failures is frequent. Therefore the development of new drugs is needed and would clearly benefit from a deeper knowledge of the glycosylation pathways of these pathogens.
Unique pathways or enzymes involved in glycans biosynthesis in parasitic and fungal pathogens are the primary focus of our researches. Our projects aim at:
- Identifying, cloning and characterising potential drug targets (ideally absent in human)
- Proving their importance for the pathogen survival, growth or virulence by targeted gene disruption approaches
- and eventually highlighting differences between human and pathogens enzymes that could be exploited for the development of a drug.
In the last years, we have identified the first proteins involved in the biosynthesis of galactofuranose containing carbohydrates in eukaryotes and demonstrated their contribution to the virulence of both the protozoan Leishmania and the fungus Aspergillus. The galactofuranose metabolism appears as an interesting target for the development of adjunct therapy against invasive aspergillosis, a severe condition affecting immunocompromised patients (Figure 1). Our studies also unravelled the UDP-galactose biosynthetic pathways in Leishmania parasites and demonstrated the involvement of an unusual UDP-sugar pyrophosphorylase in galactose salvage. The crystal structure of some of these enzymes has been elucidated and detailed mechanistic analysis performed.
december 2010
- Figure 1: The cell wall of Aspergillus fumigatus hyphae is of variable thickness but consistently thinner in galactofuranose deficient mutants. The mean values (± standard deviation) of cell wall thickness obtained from 25 measurements were 227.5 nm (± 15.98 nm) and 109.7 nm (± 11.3 nm) for wild type and the mutant respectively. The structural cell wall defect is associated with a reduced virulence and a strongly increased susceptibility to current drugs of the galactofuranose deficient fungus. Photos: Dr. Manfred Rohde, Helmholtz Centre for Infection Research, Braunschweig