Candida Infection Biology

Research of IGB's Molecular Biotechnology is focused among others on infectious diseases, taking the human pathogenic yeast Candida albicans as an example. Our goal is developing novel antimycotics to combat fungal pathogens in humans.

Fundamental research studies on host-pathogen interaction are used to help identify prime infection targets. Using both genome-wide DNA microarrays developed and produced at Fraunhofer IGB and proteome analyses of the Candida albicans cell wall, we aim to identify the molecular mechanisms of pathogenic fungi colonization and infection.

Topics and projects

Projects

ImResFun "Molecular Mechanisms of Human Fungal Pathogen Host Interaction"

I. FYI-Chip – Detection of human fungal pathogens using a lab-on-a-chip device

Infections by yeasts and mold fungi lead to severe illnesses, especially in immunocompromised patients. With a mortality rate of between 30 to 80 percent, the rapid detection of a pathogen, including its resistance spectrum, plays a particularly decisive role in the success of treatment. The classical detection of pathogens using culture-based methods is tedious and error prone. Therefore short-term test procedures are needed. The aim of the joint project is to develop a fully integrated lab-on-a-chip system (LOC) which can combine individual functional components such as sample preparation, microfluidics and the detection of pathogenic DNA within a very short time.

  • Funding: BMBF
  • Started 01/04/2011 ending 31/03/2014
  • Partner:
    Euroimmun Medizinische Labordiagnostika AG, Lübeck (coordinator)
    Heart and Diabetes Centre NRW, Bad Oeynhausen
    Institute of Interfacial Engineering IGVT, University of Stuttgart
    Multi Channel Systems MCS, Reutlingen
    Robert Bosch GmbH, Gerlingen

more details

II. Genomic Approaches to Unravel the Molecular Mechanisms of Pathogenicity in the Human Fungal Pathogen Candida glabrata - FunPath

  • Program: ERA-NET PathoGenoMics
  • Funding: BMBF
  • Started 1/2/2007, ended 31/07/2010
  • Partner:
    Karl Kuchler, Medical University Vienna
    Christoph Schüller, University of Vienna
    Christophe d’Enfert, Institut Pasteur, Paris
    Dominique Ferrandon, IBMC du CNRS, Strasbourg
    Bernhard Hube, HKI, Jena
    Toni Gabaldon, Bioinformatics Department, Valencia

The molecular mechanisms driving invasion of mammalian hosts by fungal pathogens pose many scientifically challenging problems but are as yet little understood. The availability of the entire genome sequence of the important fungal pathogen Candida glabrata (Cg) reveals striking similarities and to the non-pathogenic relative yeast Saccharomyces cerevisiae (Sc), opening the door to pursue global genomics approaches to better understand fungal pathogenicity. Cg, a commensal pathogen, accounting for the second-most frequent cause for systemic mycoses, causes up to 20% of clinical mycoses. The intrinsically high drug resistance to widely used antifungal drugs such as azoles makes Cg a real threat in infectious diseases. In contrast to Ca, relevant host immune defenses against Cg are unknown. Therefore, FunPath will address at the genome scale the question which candidate Cg genes are necessary to bypass mammalian host defense. Hence, FunPath will identify virulence mechanisms and improve our current understanding of fungal pathogenicity.

III. Dr. Jekyll and Mr. Hyde: A Systems Approach to the Therapy of Nosocomial Infections Caused by Candida albicans: A Commensal Organism Switches to a Deadly Pathogen

Program: Medical systems biology

Funding: BMBF

Started 02/09, ending on 01/12

Partner:
1. Helmholtz-Zentrum für Infektionsforschung (HZI)
Prof. Dr. Ursula Bilitewski, Target identification (TI)
Dr. Dipl-Ing. Vitor Martins dos Santos, Systems and Synthetic Biology Group (SSBI

2. Klinikum der Universität Tübingen (UT)
Prof. Dr. Martin Schaller, Universitäts-Hautklinik (HK)
PD Dr. Klaus Schröppel, Institut für medizinische Mikrobiologie und Hygiene (IMH)

4. Centre for Systems Biology; Universität Stuttgart (CSB)
Prof. Dr. – Ing. Dr. h.c. Matthias Reuss, Institut für Bioverfahrenstechnik

5. German Cancer Research Center (DKFZ)
Prof. Dr. Thomas Höfer, Research Group Modeling of Biological Systems

6. Genedata Bionformatik GmbH (GD)
Dr. Thomas Hartsch

7. Insilico Biotechnology AG (IS)

Dr.-Ing. Dirk Müller

8. BIOBASE – Biological Databases GmbH (BB) (subcontractor)
Dr. Alexander Kel

Scope and Aims of the Project

The fungus Candida albicans resides asymptomatically on the skin and the mucosa of healthy people but causes serious invasive diseases in immunocompromised patients. Whereas conventional diagnostic and therapeutic strategies focus on the identification and elimination of the pathogen, the contribution of the host is almost neglected. However, in an in vitro system it was shown that cytokines are produced by host cells in response to the presence of C. albicans and that they are essential for the protection of the host, i.e. maintenance of the commensal state of C. albicans. Removal of these cytokines, e.g. of tumor necrosis factor α (TNFaα), lead to the destruction of the epithelial layer by invading C. albicans. However, the precise protective mechanisms are not yet identified, but are related to the enhanced expression of toll-like receptor 4 (TLR4) and probably to the secretion of antimicrobial peptides by host cells. Thus, it is anticipated that an improved understanding of the protective and defense mechanisms of the host will lead to new diagnostic biomarkers and also to new therapeutic strategies. As illustrated in the scheme below, this project will focus in a multidisciplinary, integrated approach on host-pathogen interactions by assessing under commensal and pathogenic conditions, from a Systems Biology perspective, both the immune response of the host to the presence of the opportunistic pathogen and the response of the pathogen to the host.

IV. Novel drugs against fungal human pathogens: From known leads and novel screening tools via target identification to first investigations for preclinical studies

The Fraunhofer IGB identifies and characterizes new antimycotically effective substances in cooperation with EMC microcollections GmbH (EMC), the Helmholtz Center for Infection Research, and the Tübingen University Hospital. For this purpose, the Activity Selectivity Assay (AS-HTS), which was developed at our institute, is used for the screening of extensive substance libraries, which are synthesized by our project partner EMC and made available for this work.