A3: Induction and regulation of Coxiella burnetii persistence by microenvironmental factors

A3: Induction and regulation of Coxiella burnetii persistence by microenvironmental factors

Coxiella (C.) burnetii is the causative agent of the zoonotic disease Q fever, which can be either acute or chronic. While acute Q fever is a flu-like illness, chronic Q fever mainly manifest as a potentially life-treating endocarditis month or years after primary infection. The period prior outbreak of chronic Q fever is characterized by bacterial persistence, a physiologically dormant state that can cause relapsing infections and antibiotic resistance. Currently, it is unknown how C. burnetii persistence is induced or regulated.
We hypothesize that micromilieu factors are decisive for C. burnetii persistence and that different cell types provide diverse microenvironments. Accordingly, the project aims to characterize the induction of C. burnetii persistence under varying oxygen and tonicity conditions and to investigate the host cell metabolism, signaling and immune response of C. burnetii infected human macrophages and endothelial cell lines.

Lührmann Schmema

In macrophages C. burnetii are unable to replicate under hypoxic conditions. Hypoxia induces the stabilization of HIF1α, which in turn reduces the activation of STAT3. This leads to reduction of the TCA metabolite citrate, and a subsequent inhibition of C. burnetii replication (Hayek et al. 2019, Cell Reports). In contrast, C. burnetii replicates equally well in normoxic and hypoxic endothelial cells. The underlying reason is unclear.

Supervisor