Fabian Fischer


B8 Functional analysis of Coxiella burnetii effector proteins

Principal investigator
Anja Lührmann and Jonathan Jantsch

Roland Lang

Influence of hypoxia on macrophage-C. burnetii interaction

The Gram-negative obligate intracellular pathogen Coxiella burnetii is the causative agent of the zoonosis Q-fever. Most common reservoirs for C. burnetii are cattle, sheep or goats. Human infection usually occurs through inhalation of aerosolized soil or animal products contaminated with infectious doses as low as one  bacterium. Whereas acute Q-fever is characterized by flu-like symptoms that can develop into pneumonia or hepatitis, chronic disease can lead to severe endocarditis with fatal outcome.
Main targets of C. burnetii are monocytes and macrophages. After uptake, the pathogen resides in a large phagolysosomal-like vacuole, permissive for bacterial replication. For the establishment and maintenance of this replicative vacuole the translocation of effector proteins into the host cells by the type IV secretion system (T4SS) is essential. However, it is unknown which physiological condition favours bacterial replication within the C. burnetii-containing vacuole. Importantly, C. burnetii grown in liquid media requires low oxygen concentration for replication. Tissue hypoxia is prevalent in many physiological and pathological conditions such as inflammation and infection. Thus, hypoxia might also affect the interplay of macrophages and Coxiella burnetii facilitatingthe formation of a niche wherethe bacteria can persist and thereby influence the outcome of the disease.
The specific aims of my MD thesis are to test the impact of hypoxia on (1) intracellular survival and (2) on formation of the Coxiella-containing vacuole in murine macrophages.This study may contribute to further understanding of Q-fever pathogenesis and treatment.

Figure: Infected macrophages cultured under normoxic (21% O2, left) and hypoxic (0,5% O2, right) conditions. Green = Coxiella burnetii, blue = DAPI





July 2014 6th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
"Hypoxia inhibits Coxiella burnetii growth in Macrophages"