Dr. Jekyll and Mr. Hyde

A Systems Approach to the Therapy of Nosocomical Infections caused by Candida albicans – A commensal Organism switches to a deadly Pathogen

The project is part of the BMBF-Funding Initiative "Medical Systems Biology"
Funding Period:

2009 - 2012

Project description

Candida albicans is the single most important human fungal pathogen, causing up to 70 % of all fungal nosocomial infections. Although this fungus usually is a commensal and frequently found on the skin and mucosa of healthy humans, it often becomes  a threatening pathogen in patients with a compromised immune system. As most C. albicans  infections are caused by strains that already colonized the patient and not by those acquired in the hospital, occasionally antimycotics are given prophylactically to prevent the outbreak of the infection.

However, this regime leads to selection of resistant strains and does not take into account the individual predisposition of the patient. Thus, new tools for the identification of patients at risk and new diagnosis and therapeutic strategies are needed. However, knowledge of molecular mechanisms and underlying networks leading to the protection of the host from an infection, i.e. lock the opportunistic fungus in the commensal state, is still in its infancy, but would lead to the identification of biomarkers, which indicate the risk of a patient to acquire a C. albicans infection. Therefore, this project aims at generating a systems understanding of the key mechanisms leading to the protection of the host by preventing the pathogenic state of C. albicans. The interdisciplinary consortium of universities, research institutes, clinics and SMEs will focus on the study of host-pathogen interactions by assessing, from a Systems Biology perspective, both the response of the host to Candida albicans, and of this opportunistic pathogen to the host under commensal and pathogenic conditions. While assisting in experimental design, data interpretation and hypothesis generation, a multi-scale modeling framework capturing the key features of the interaction of Candida albicans with host (epithelial)cells and of its switch from a commensal to a pathogen will be developed, experimentally tested and iteratively refined. Modelling and experimentation are intertwined at all stages of the project.It is anticipated that this multidisciplinary, integrated approach will lead to the identification of new diagnostic biomarkers and, ultimately, to novel intervention strategies against infections by commensal organisms such as Candida albicans.

Ursula Bilitewski, Vitor Martins dos Santos

Helmholtz-Zentrum für Infektionsforschung (HZI)

Martin Schaller, Klaus Schröppel

Klinikum der Universität Tübingen (UT), Universitäts-Hautklinik (HK), Institut für medizinische Mirkobiologie und Hygiene (IMH)

Steffen Rupp, Kai Sohn

Fraunhofer-Institut für Grenzflächen und Bioverfahrenstechnik (IGB) Dep. Molecular Biotechnology Functional Geneomics Group

Matthias Reuss

Centre for Systems Biology (CSB), University of Stuttgart

Thomas Höfer

German Cancer Research Center (DKFZ) Modeling of Biological Systems

Thomas Hartsch

Gendata Bioinformatik GmbH

Dirk Müller

Insilico Biotechnology AG (IS)

Alexander Kel

BIOBASE – Biological Databases GmbH (BB)

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