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

Metabolic adaptation reactions are common when prokaryotes interact with eukaryotic cells, especially when the bacteria are internalized by these host cells. Such adaptations lead to significant changes in the metabolism of both partners. While the final outcome may be sometimes beneficial (e.g., in case of insect endosymbiosis) or (mainly) neutral for the interacting partners (e.g., microbiota and their hosts) (1 – 3), it is usually detrimental in infections of mammalian cells by intracellular bacterial pathogens. In this encounter, a host cell-defense program is initiated, including antimicrobial metabolic reactions aimed to damage the invading pathogen and/or to withdraw essential nutrients, while the intracellular pathogen tries to deprive nutrients from the host cell and to counteract the antimicrobial reactions, resulting in damaging of the host cell. Our knowledge of the metabolic adaptation processes occurring during this liaison and the link between these metabolic changes and the pathogenicity is still rather fragmentary. For these complex metabolic interactions, we coin the term "pathometabolism". Studies of pathometabolism are not only central for a deeper understanding of bacterial infections caused by intracellular bacterial pathogens, but may also provide promising bacterial and host cell targets for the development of novel antimicrobial therapeutic measures.