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- Title
Evolved bacterial resistance against fluoropyrimidines can lower chemotherapy impact in the Caenorhabditis elegans host.
- Authors
Rosener, Brittany; Sayin, Serkan; Oluoch, Peter O.; García González, Aurian P.; Hirotada Mori; Walhout, Albertha J. M.; Mitchell, Amir
- Abstract
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.
- Subjects
DRUG metabolism; FLUOROPYRIMIDINES; DRUG toxicity; BACTERIAL evolution; CANCER chemotherapy; CAENORHABDITIS elegans; DRUG resistance in bacteria
- Publication
eLife, 2020, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.59831