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Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Metabolic Adaptations of Intracellullar Bacterial Pathogens and their Mammalian Host Cells during Infection
Wolfgang Eisenreich1, Jürgen Heesemann2, Thomas Rudel3
1Lehrstuhl für Biochemie, Technische Universität München, Germany.
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.
Insights
Intracellular bacterial pathogens manipulate host cell metabolism for replication. Understanding these metabolic adaptations and host responses is crucial for developing new antibacterial therapies.
Area of Science:
- Microbiology
- Cell Biology
- Metabolic Engineering
Background:
- Intracellular bacterial pathogens invade host cells, causing severe infections.
- Pathogen-host interactions trigger complex metabolic adaptations for pathogen proliferation.
- Bacterial metabolism and virulence gene expression are linked during intracellular replication.
Purpose of the Study:
- To review nutrients and metabolic pathways used by intracellular pathogens.
- To explore links between bacterial metabolism and virulence gene expression.
- To discuss pathogen-induced metabolic responses in host cells and their implications for therapy.
Main Methods:
- Literature review of metabolic pathways in intracellular pathogens.
- Analysis of host cell metabolic responses to bacterial infection.
- Discussion of virulence factors and their metabolic impact.
Main Results:
- Intracellular pathogens utilize specific nutrients and metabolic pathways for replication.
- Bacterial metabolism influences virulence gene expression.
- Pathogens can trigger significant changes in host cell carbon and nitrogen metabolism.
Conclusions:
- Knowledge of host-pathogen metabolic interactions can inform novel antibacterial strategies.
- Established cell lines may not accurately reflect in vivo metabolic responses.
- Developing more relevant host cell models is essential for understanding infection and therapy.
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