Pathogen-host interactomes and signalling complexes in bacterial infections

  • Prof. Dr. Thomas Rudel, Lehrstuhl für Mikrobiologie, Universität Würzburg

Project Partners:
  • Prof. Dr. Rainer Haas, Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, LMU München
  • Prof. Dr. Michael Hensel, Mikrobiologie, Universität Osnabrück
  • Prof. Dr. Hubert Hilbi, Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, LMU München
  • Prof. Dr. Thomas F. Meyer, Max-Planck-Institut für Infektionsbiologie, Berlin
  • Prof. Dr. Ulrich Schaible, Forschungszentrum Borstel
  • PD Dr. Matthias Wilmanns, EMBL Hamburg
  • Prof. Dr. Michael Hecker & Prof. Dr. Dörte Becher, Institut für Mikrobiologie, Ernst-Moritz-Arndt-Universität Greifswald

During the course of infection, intracellular bacterial pathogens can dramatically alter host cell function to overcome innate and aquired immune responses and to inhabit their preferred niches. Due to the intimate contact between host and pathogen, many bacterial pathogens have evolved strategies to directly interact with their host. For instance, secreted bacterial proteins either decorating the pathogen-containing vacuoles (PCVs) or injected into the host cell directly bind to host proteins and thereby influence their activity. Although generally recognized as crucial for the infection process and subsequent pathogenesis, very few interactions between bacterial and host molecules have yet been investigated. The low abundance of these infection-related pathogen-host protein heterocomplexes presents a major challenge for their investigation at a global level.
Thus, we have initiated a consortium of experts that proposes the investigation of the pathogen-host interactome of the etiological agents for a range of important human infections such as typhoid fever, tuberculosis, trachoma, Legionnaires? disease, gastritis and peptic ulcer diseases. For the investigation of the interactions between bacterial effectors and host structures on a global scale we will use affinity purification via phagosome-associated bacterial or host proteins combined with density gradients to isolate phagosomal membranes containing bacterial-host cell factor complexes. In addition, host proteins associated with individual bacterial factors will be isolated by co-immunoprecipitation. Proteome and lipidome analysis of these purified fractions by highly sensitive quantitative high-throughput mass spectrometry will identify all putative host factors interacting with bacterial phagosomes and secreted proteins. The interaction of the identified factors will be further validated and their significance in virulence will be accessed by RNA interference (RNAi)-based loss-of-function analyses. These global studies will not only identify interactions relevant for bacterial pathogenesis but also potential therapeutic targets.

Immunofluorescence staining of Chlamydia trachomatis inclusions (red) at 24 hours post infection in HeLa229 epithelial cells.

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