Journal article
Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function
Massachusetts Institute of Technology1
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
Network Reconstruction in Silico Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3
iLoop, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
Big Data 2 Knowledge, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect either treatment efficacy or immune function.
Here, we quantify local metabolic changes in the host microenvironment following antibiotic treatment for a peritoneal Escherichia coli infection. Antibiotic treatment elicits microbiome-independent changes in local metabolites, but not those distal to the infection site, by acting directly on host cells.
The metabolites induced during treatment, such as AMP, reduce antibiotic efficacy and enhance phagocytic killing. Moreover, antibiotic treatment impairs immune function by inhibiting respiratory activity in immune cells. Collectively, these results highlight the immunomodulatory potential of antibiotics and reveal the local metabolic microenvironment to be an important determinant of infection resolution.
Language: | English |
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Year: | 2017 |
Pages: | 757-765 |
ISSN: | 19346069 and 19313128 |
Types: | Journal article |
DOI: | 10.1016/j.chom.2017.10.020 |
ORCIDs: | Palsson, Bernhard |
Animals Anti-Bacterial Agents Disease Models, Animal Escherichia coli Infections Immunologic Factors LC-MS/MS Metabolome Metabolomics Mice, Inbred C57BL Microbial Viability Mitochondria Peritonitis Phagocytosis antibiotic germ-free immunomodulation metabolic environment metabolomics phagocytosis respiration systems biology