Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function
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nihms917699.pdf
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Author(s)
McCloskey, Douglas
Palsson, Bernhard O.
Yang, Jason Hung-Ying
Saluja, Prerna Bhargava
Mao, Ning
Collins, James J.
Date Issued
December 2017
Journal
Cell Host & Microbe
Publisher
Elsevier BV
Citation
Yang, Jason H., Prerna Bhargava, Douglas McCloskey, Ning Mao, Bernhard O. Palsson, and James J. Collins. “Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function.” Cell Host & Microbe 22, no. 6 (December 2017): 757–765.e3. © 2017 Elsevier Inc.
Version
Final published version
Abstract
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. Antibiotic susceptibility is sensitive to metabolites, but how this affects in vivo treatment efficacy remains unexplored. Yang, Bhargava et al. characterize antibiotic-induced changes to the metabolic environment during infection and find that direct actions of antibiotics on host cells induce metabolites that impair drug efficacy and enhance phagocytic activity.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CHOM.2017.10.020
