Metabolic host responses to infection by intracellular bacterial pathogens

Abstract

The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies.

Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

“…Metabolic host responses to bacterial infections favor survival and are important in the pathogenic process (78). The relative abundances of proteins involved in arginine metabolism and citrulline synthesis, namely, arginine deiminase (HMPREF0389_ 01584), acetyl ornithine transferase (HMPREF0389_01570) (36), aminotransferase (HMPREF0389_01352 and HMPREF0389_ 01353), amidotransferase family protein (HMPREF 0389_00349), arginine-tRNA ligase (HMPREF0389_00390), and arginine decarboxylase (HMPREF0389_00102), indicate that the nutritional needs of the bacteria are met during infection.…”

Subversion of Cell-Autonomous Host Defense by Chlamydia Infection

“…The mechanisms how the innate immune system, the cell-autonomous defense, and host cell death affect chlamydial infection have gained significant attention over the past years and many of the central signaling pathways have meanwhile been elucidated. It is currently unclear if and, when indicated, how all these central lines of defense against intracellular pathogens are connected to the metabolic status of the cell (Eisenreich et al 2013). This connection may be particularly relevant in the case of an obligate intracellular pathogen such as Chlamydia that is-in its dependence-closely connected to the host metabolism.…”

The Immune Deficiency Pathway Regulates Metabolic Homeostasis inDrosophila

“…However, microbial detection initiates a complex spectrum of physiological responses, that may include elements as diverse as increased body temperature, lethargy, loss of appetite, social isolation, and tolerance mechanisms that neutralize pathogens without affecting their numbers (Ayres and Schneider, 2012). Metabolic adaptations are common to host responses to infection (Eisenreich et al, 2013). In this case, hosts balance their traditional metabolic needs against the immediate threat presented by the microbe, and frequently alter metabolic pathway activity accordingly.…”