Evolved bacterial resistance against fluoropyrimidines can lower chemotherapy impact in the Caenorhabditis elegans host
Authors
Rosener, BrittanySayin, Serkan
Oluoch, Peter O.
Garcia-Gonzalez, Aurian
Mori, Hirotada
Walhout, Albertha J. M.
Mitchell, Amir
UMass Chan Affiliations
Graduate School of Biomedical SciencesDepartment of Molecular, Cell and Cancer Biology
Program in Molecular Medicine
Program in Systems Biology
Document Type
Journal ArticlePublication Date
2020-11-30Keywords
C. elegansE. coli
chemotherapy
computational biology
drug adaptation
drug resistance
evolutionary adaptation
microbiome
systems biology
Bacteria
Computational Biology
Molecular Biology
Systems and Integrative Physiology
Systems Biology
Metadata
Show full item recordAbstract
Metabolism of host-targeted drugs by the microbiome can substantially impact host treatment success. However, since many host-targeted drugs inadvertently hamper microbiome growth, repeated drug administration can lead to microbiome evolutionary adaptation. We tested if evolved bacterial resistance against host-targeted drugs alters their drug metabolism and impacts host treatment success. We used a model system of Caenorhabditis elegans, its bacterial diet, and two fluoropyrimidine chemotherapies. Genetic screens revealed that most of loss-of-function resistance mutations in Escherichia coli also reduced drug toxicity in the host. We found that resistance rapidly emerged in E. coli under natural selection and converged to a handful of resistance mechanisms. Surprisingly, we discovered that nutrient availability during bacterial evolution dictated the dietary effect on the host - only bacteria evolving in nutrient-poor media reduced host drug toxicity. Our work suggests that bacteria can rapidly adapt to host-targeted drugs and by doing so may also impact the host.Source
Rosener B, Sayin S, Oluoch PO, García González AP, Mori H, Walhout AJ, Mitchell A. Evolved bacterial resistance against fluoropyrimidines can lower chemotherapy impact in the Caenorhabditis elegans host. Elife. 2020 Nov 30;9:e59831. doi: 10.7554/eLife.59831. PMID: 33252330; PMCID: PMC7725501. Link to article on publisher's site
DOI
10.7554/eLife.59831Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41663PubMed ID
33252330Related Resources
Rights
Copyright Rosener et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.59831
Scopus Count
Except where otherwise noted, this item's license is described as Copyright Rosener et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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