Metabolic Adaptations of Intracellullar Bacterial Pathogens and their Mammalian Host Cells during Infection (“Pathometabolism”)

Abstract

ABSTRACT Several bacterial pathogens that cause severe infections in warm-blooded animals, including humans, have the potential to actively invade host cells and to efficiently replicate either in the cytosol or in specialized vacuoles of the mammalian cells. The interaction between these intracellular bacterial pathogens and the host cells always leads to multiple physiological changes in both interacting partners, including complex metabolic adaptation reactions aimed to promote proliferation of the pathogen within different compartments of the host cells. In this chapter, we discuss the necessary nutrients and metabolic pathways used by some selected cytosolic and vacuolar intracellular pathogens and - when available - the links between the intracellular bacterial metabolism and the expression of the virulence genes required for the intracellular bacterial replication cycle. Furthermore, we address the growing evidence that pathogen-specific factors may also trigger metabolic responses of the infected mammalian cells affecting the carbon and nitrogen metabolism as well as defense reactions. We also point out that many studies on the metabolic host cell responses induced by the pathogens have to be scrutinized due to the use of established cell lines as model host cells, as these cells are (in the majority) cancer cells that exhibit a dysregulated primary carbon metabolism. As the exact knowledge of the metabolic host cell responses may also provide new concepts for antibacterial therapies, there is undoubtedly an urgent need for host cell models that more closely reflect the in vivo infection conditions.