Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function
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 t...
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| Format: | Article |
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Elsevier BV
2019
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| Online Access: | http://hdl.handle.net/1721.1/120132 https://orcid.org/0000-0003-0921-4657 https://orcid.org/0000-0002-5560-8246 |
| _version_ | 1826208164685545472 |
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| author | McCloskey, Douglas Palsson, Bernhard O. Yang, Jason Hung-Ying Saluja, Prerna Bhargava Mao, Ning Collins, James J. |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science McCloskey, Douglas Palsson, Bernhard O. Yang, Jason Hung-Ying Saluja, Prerna Bhargava Mao, Ning Collins, James J. |
| author_sort | McCloskey, Douglas |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:01:33Z |
| format | Article |
| id | mit-1721.1/120132 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:01:33Z |
| publishDate | 2019 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1201322022-09-28T17:48:32Z Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function McCloskey, Douglas Palsson, Bernhard O. Yang, Jason Hung-Ying Saluja, Prerna Bhargava Mao, Ning Collins, James J. Institute for Medical Engineering and Science Massachusetts Institute of Technology. Department of Biological Engineering Yang, Jason Hung-Ying Saluja, Prerna Bhargava Mao, Ning Collins, James J. 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. United States. Defense Threat Reduction Agency (Grant HDTRA1-15-1-0051) National Institutes of Health (U.S.) (Grant U01AI124316) National Institutes of Health (U.S.) (Grant K99GM118907) Novo Nordisk Foundation (Grant NNF16CC0021858) Paul G. Allen Frontiers Group Wyss Institute for Biologically Inspired Engineering 2019-01-24T21:55:37Z 2019-01-24T21:55:37Z 2017-12 2018-12-19T16:08:29Z Article http://purl.org/eprint/type/JournalArticle 1931-3128 http://hdl.handle.net/1721.1/120132 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. https://orcid.org/0000-0003-0921-4657 https://orcid.org/0000-0002-5560-8246 http://dx.doi.org/10.1016/J.CHOM.2017.10.020 Cell Host & Microbe Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | McCloskey, Douglas Palsson, Bernhard O. Yang, Jason Hung-Ying Saluja, Prerna Bhargava Mao, Ning Collins, James J. Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function |
| title | Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function |
| title_full | Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function |
| title_fullStr | Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function |
| title_full_unstemmed | Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function |
| title_short | Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function |
| title_sort | antibiotic induced changes to the host metabolic environment inhibit drug efficacy and alter immune function |
| url | http://hdl.handle.net/1721.1/120132 https://orcid.org/0000-0003-0921-4657 https://orcid.org/0000-0002-5560-8246 |
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