Stephanie Bisle

Suche


B8 Functional analysis of Coxiella burnetii effector proteins

Principal investigator
Anja Lührmann

Mentor
Christian Berens

PhD exam: 11.01.2016

Characterization of host cell pathways altered by effectors of Coxiella: identification of novel therapeutic targets effector proteins

Coxiella burnetii is a small, intracellular Gram negative pathogen and the causative agent of Q fever, a zoonotic disease. Main reservoirs of the bacterium are farm animals, such as cattle, goats and sheep but also include birds and pets as well as arthropods.
Transmission to humans mainly occurs through inhalation of contaminated aerosols. C. burnetii is highly infectious and except of New Zealand outbreaks of Q fever are reported worldwide. The disease either manifests as acute or chronic form. Acute Q fever presents as a mild flu-like illness but can develop into pneumonia and hepatitis. Chronic Q fever often results in endocarditis and cases often have a fatal outcome. Upon uptake by alveolar monocytic phagocytes C. burnetii induces the formation of a parasitophorous vacuole by fusion with the host's early and late endosomes as well as with the host's cell lysosome. The parasitophorous vacuole is not distinguishable from a secondary lysosome and is characterized by an acidic pH (4,5 - 5,5), the presence of acid hydrolases and cationic peptides. The bacterium requires this environment in order to replicate.
It has been shown that during infection of host cells C. burnetii expresses a type IV secretion system (T4SS) which is homologous to the T4SS of the intracellular pathogen L. pneumophila. The T4SS is essential for the intracellular replication of C. burnetii and its survival in the host cell. It is believed that effector proteins translocated by the T4SS modulate host cell pathways in order to enable bacterial survival and replication. However, the function of the so far identified 60 Coxiella burnetii effector proteins is largely unknown.
In this project novel C. burnetii effector proteins are to be analyzed on their role in interfering and modulating host cell pathways. Main objectives are to identify host cell signalling pathways which are targeted by these effector proteins and to understand their mode of action at molecular and cellular level in order to establish their physiological relevance. The findings are to be correlated to the expression and sequence variability of these effector proteins amongst different strains and clinical isolates of C. burnetii.
Furthermore the knowledge gained will be correlated with findings obtained in studies on novel effector proteins of the intracellular pathogens Chlamydia and Brucella. As an overall aim these studies are to give further insight into the function of novel effector proteins and their role in interfering with particular eukaryotic cell processes. At long sight this is to help identifying possible novel targets for therapeutic intervention.

Figure: Parasitophorous vacuole in MEF cells infected with C. burnetii for seven days C. burnetii are shown by immunostaining with a specific anti-Coxiella antibody (green) and the host cell nucleus is stained with DAPI (blue). Picture provided by R. Eckart.

 

Publications

Eberhardt, A., Hoyland, C. N., Vollmer, D., Bisle, S., Cleverley, R. M., Johnsborg, O., Havarstein, L. S., Lewis, R. J. and Vollmer, W. (2012) Attachment of Capsular Polysaccharide to the Cell Wall in Streptococcus pneumoniae. Microb Drug Resist 18(3), 240-255.

 

 

Presentations

 

October 2014 66. Jahrestagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie, Dresden, Germany
The KEKE motif of the C. burnetii T4SS effector protein CaeA is important to maintain the anti-apoptotic effect
Poster
     
July 2014 6th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
“The KEKE motif of the C. burnetii T4SS effector protein CaeA is important to maintain the anti-apoptotic effect”
Talk
     
July 2013 5th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
Use of inducible cell lines to analyze the function of single Coxiella burnetii effector proteins
Talk
     
June 2013 CELLPATH'meeting ERA-NET PathoGenoMics 3rd call project, Lisbon, Portugal
Molecular characterization of the Coxiella burnetii T4SS effector protein CaeA
Talk
     
September 2012 64. Jahrestagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie, Hamburg, Germany
Generation of an inducible expression system to analyze the function of a single Coxiella burnetii T4SS effector protein
Poster
     
July 2012 4th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
Generation of an inducible expression system to analyze the function of a single Coxiella effector protein
Poster
     

 

Awards

Best Poster Award

first place

66. Jahrestagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie, Hamburg, Germany, October 2014
The KEKE motif of the C. burnetii T4SS effector protein CaeA is important to maintain the anti-apoptotic effect

Best Talk Award

third place

6th Annual Retreat, Erlangen School of Molecular Communication Kloster Banz, Bad Staffelstein, Germany, July 2014
“The KEKE motif of the C. burnetii T4SS effector protein CaeA is important to maintain the anti-apoptotic effect”