Metabolic cross-talk between Bartonella henselae and host cells

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Slow growing humapathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders (bacillary angiomatosis). The facultative intracellular pathogen replicates rapidly within endothelial host cells suggesting that these cells represent an ecological niche supplying the bacterium with oxygen and nutrients. On the other hand, infections with B. henselae result in the activation of hypoxia-inducible factor (HIF)-1, the key transcription factor involved in host cell metabolism (glycolysis, oxygen supply via angiogenesis, and erythropoiesis). Preliminary experiments revealed that B. henselae do not replicate in endothelial cells with a HIF-1 knock-down. Additionally, we identified several B. henselae genes crucial for intracellular survival. Using cell culture models, we now want to analyze how the intracellular growth and persistence of the facultative intracellular pathogen B. henselae depends on HIF-1 activity. For this purpose, we have generated several HIF-1 knock down endothelial cell lines (using hairpin siRNA) and established methods for analyzing intracellular oxygen levels and HIF-1 activation pathways. Moreover, a novel Bartonella-liquid growth medium allows us to investigate which biological compounds (e.g. sucrose, amino acids) are required for the growth and persistence of B. henselae in host cells. The results of our investigations should (i) help to understand the metabolic cross-talk between intracellular bacteria (e.g. B. henselae) and their host cells on a molecular and cellular level and (ii) should possibly result in new therapeutic strategies for the treatment of infections with intracellular bacteria.