SFB796 - Joint project 01

Suche


Studying anti-apoptotic mechanisms of effector proteins from plant and human pathogens in the heterologous system

 

Project summary

Many pathogens exert control on processes that regulate cell death, since abrogation of host cell death is often beneficial for the pathogen and facilitates successful replication. The induction of Programmed Cell Death (PCD) is a genetically controlled and conserved process in eukaryotic cells. Interestingly, heterologous regulators, such as Bax and BI-1, exist suggesting that there might be a conserved cell death switching mechanism across kingdoms. Coxiella burnetii, is a Gram-negative, obligate intracellular zoonotic pathogen that causes Q-fever. Inhibition of host cell death is important for the slow growing bacteria C. burnetii to replicate and to establish a successful infection. C. burnetii uses a type IV secretion system to deliver over 130 effector proteins into the host cell. So far, three of them were shown to supress host cell apoptosis, a PCD pathway. Among those is CaeB which was shown to inhibit mitochondrial outer membrane permeabilisation (MOMP) upon s taurosporine induced cell death in HEK293 cells, while targeting of Bax to mitochondria was not affected, indicating that CaeB inhibits apoptosis at the mitochondrial level. The aim of our work is to use CaeB as a tool to dissect the cell death pathway in plants and in mammalian cells. To this end we analysed the ability of CaeB to suppress PCD in plants and showed that CaeB decelerates development of cell death symptoms elicited either by Bax or the interaction between the R-gen Pto and the corresponding avirulence gene AvrPto. Ectopic expressed green fluorescence protein (GFP) tagged CaeB localised mainly to the ER in planta. Importantly, in planta CaeB also suppressed tunicamycin trigger ER stress. These results demonstrate that CaeB is a across kingdom cell death suppressor and indicates that there is a crosstalk between mitochondria and ER during cell death induction. In the future we aim to pursue the investigation of the molecular activity of CaeB and the interaction of the ER with the mitochondria to induce cell death.